Inflammatory Spinal Disorders: Clinical Guidelines

List of Abbreviations

ANR — Association of Neurosurgeons of Russia

ATOR — Association of Trauma Surgeons and Orthopedists of Russia

BF - biofeedback

VAS — visual analog scale

CI — confidence interval

SSI — surgical site infection

SSIs — spine surgical site infection

CT — computed tomography

AFB — acid-fast bacilli

PT — physical therapy

MTB - Mycobacterium tuberculosis

MDR — multidrug resistance

MRI — magnetic resonance imaging

NAF — National Association of Phthisiologists

NSP — nonspecific osteomyelitis of the spine

FSU — functional spinal unit

ATT — antituberculosis chemotherapy

RAF — Russian Association of Phthisiologists

CRP — C-reactive protein

SEA — spinal epidural abscess

US — ultrasound examination

PRM — physical and rehabilitation medicine

PT — physiotherapeutic treatment

TENS — transcutaneous electrical nerve stimulation

XDR — extensively drug-resistant

ECG — electrocardiography

AOSpine — global association of spine care professionals

ASIA — American Spinal Injury Association

FIM — Functional Independence Measure

RASS — Russian Association of Spine Surgeons

SSIs — Surgical Site Infection in Spinal surgery

Terms and Definitions

Arachnoiditis - inflammatory lesion of the arachnoid mater of the spinal cord

Discitis - inflammatory lesion of the intervertebral disc

Psoitis - inflammatory lesion of the psoas muscle

Psoas abscess - purulent-inflammatory lesion of the psoas muscle

Spinal meningitis - inflammatory lesion of the spinal meninges

Spinal subdural abscess - purulent-inflammatory lesion of the spinal subdural space

Spinal epidural abscess - purulent-inflammatory lesion of the epidural space of the spinal canal

Spondylitis - general term for inflammatory lesions of the vertebrae, syn. spinal osteomyelitis

Spondylodiscitis - inflammatory lesion of the intervertebral disc and vertebral bone structures

Spondylarthritis - inflammatory lesion of the zygapophysial joints

Epiduritis - inflammatory lesion of the epidural space

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Inflammatory infectious diseases of the spine – an etiologically heterogeneous group of diseases characterized by lesions of the vertebral bodies, intervertebral discs, ligamentous apparatus, and intervertebral joints, including infectious lesions caused by any bacterial agent, or occurring as a complication of surgery or manipulation on the spine (postoperative, post-manipulation).

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Etiology. Infectious (hematogenous, incl. specific and nonspecific), non-infectious (autoimmune, autoinflammatory) spondylitis, and spondylitis developing after surgical manipulations are distinguished (Fig. 1) [1].

Figure 1. Etiopathogenetic classification of spondylitis

Infectious spondylitis may be associated with hematogenous (septic) or contact spread, or be post-traumatic or post-manipulative (associated with prior surgical or anesthetic manipulations on the spine) [2 - 8]. The source of infection is any acute or chronic infectious process (carious teeth, ENT infection, phlegmon, endocarditis, bedsores, etc.), as well as penetrating injuries, including gunshot and iatrogenic ones [9, 10].

The causative agent of nonspecific spondylitis is isolated from the blood in 20 - 40% of patients [11-17]:

• gram-positive (gram+) cocci are the most common flora (up to 2/3 of cases), with Staphylococcus predominating. The most pathogenic are coagulase-positive strains Staph. aureus, Staph. intermedius, and among coagulase-negative strains, Staph. epidermidis [11-14];

• gram-negative (Gram-) flora - 1/3 of cases; Escherichia coli (10.5%), Proteus spp. (6.7%), and Pseudomonas aeruginosa (5.7%) predominate [15-17].

The most frequent causative agent of granulomatous spondylitis (90%) is M. tuberculosis complex. Parasitic (most often echinococcal) and mycotic lesions are detected less frequently; rare pathogens include Salmonella, Campylobacter, nontuberculous mycobacteria, Bacteroides, brucellosis, etc. [18 - 19]. The role of mycotic infection (most often aspergillosis) increases in immunodeficient states; in HIV infection, mycoses are considered their markers. In HIV-positive patients, the risk of generalization of mycobacterial infection increases [20].

1.3 Epidemiology of the Disease or Condition

The incidence of infectious spondylitis is 1.0 ÷ 2.5 cases per 100,000 population; in the structure of purulent-inflammatory diseases of the skeleton, it is 4 ÷ 8%. From 5.8 to 14.6% of cases are complicated by sepsis, and 1.2 ÷ 8% lead to fatal outcomes [16, 17, 21, 22].

1.4 Features of Coding the Disease or Condition

According to ICD-10, inflammatory lesions of the spine are classified by syndromic and/or etiological principle. The combination of spondylitis and inflammatory diseases of the central nervous system (myelitis, meningitis, epidural abscesses) is coded separately. When the infectious agent is verified, its specifying codes are given only as additions to the main ones.

ICD-10 codes applicable for inflammatory lesions of the spine are presented in Table 1.

Table 1. ICD-10 codes acceptable for inflammatory lesions of the spine

Comment. Autoinflammatory and autoimmune conditions are not covered in these guidelines.

1.5 Classification of the disease or condition

The main classification criteria determining the treatment strategy for a patient with infectious spondylitis: etiopathogenesis (I), type of organ and tissue inflammatory response (II), anatomical location of the lesion (III), extent of destruction (IV), disease duration (V), and presence of complications (VI) [1, 23, 24]:

I. Etiopathogenesis. See Section 1.2;

II. Type of inflammatory response. Inflammation may present as edema or destruction (focal or diffuse). In infectious spondylitis, alterative-necrotic, exudative, or proliferative (productive) variants of the inflammatory response can occur; non-specific bacterial lesions are characterized by infiltrative and diffuse changes, whereas specific lesions are characterized by focal destructions with exudative-necrotic involvement.

III. Location of the lesion. About 50% of spondylitis cases are localized in the lumbar spine, 25% in the thoracolumbar spine, 20% in the thoracic spine, and 5% in the cervical spine [6]. In 10% of cases, vertebrae in different spinal regions are simultaneously affected.

IV. Extent of spondylitis determines the number of affected vertebrae or vertebral motion segments (VMS) (Table 2)

Table 2. Classification of infectious spinal lesions based on the extent of involvement

V. Disease duration ("acuteness"). A non-specific process is considered acute if the duration of spondylitis is less than 2 months (60 days), subacute if from 2 to 6 months; a chronic course is established when the duration exceeds 6 months. A diagnosis of "chronic" spondylitis can also be established based on either of two criteria that do not directly correlate with disease duration: morphological — a predominantly alterative-necrotic type of inflammation, or clinical — the presence of sequestra or fistulae. Specific (granulomatous) spondylitis typically has a primary chronic course, with a process of less than 12 months' duration considered "clinically active" and more than 12 months considered "chronically progressing".

Complications of inflammatory spinal lesions are presented in Table 3.

Table 3. Complications of inflammatory spinal lesions

The most reproducible and tactically sound classification for the treatment of acute non-specific spondylitis/spondylodiscitis is based on the criteria of visualized vertebral destruction, associated mechanical instability of the spine, presence of an epidural component, and neurological disorders [25]. Considering the combination of features, three types of lesions are distinguished; subtypes are used to detail the choice of tactical options:

type A — a process without profound destruction, mechanical instability, neurological disorders, or epidural abscess. Includes isolated intervertebral disc involvement (discitis, A1), superficial vertebral destruction (spondylodiscitis, A2), as well as limited (A3) or pronounced (A4) involvement of paraspinal tissues;

type B — spondylodiscitis with pronounced bone destruction (B1), including paraspinal abscesses (B2) and/or local kyphosis greater than 25° as a manifestation of mechanical spinal instability (B3). Epidural abscess and neurological disorders are absent;

Type C — lesions with epidural spread, including those without neurological complications (C1), or accompanied by signs of instability (C2), neurological disorders (C3), or a combination thereof (C4).

1.5.1. Classification of surgical site infections following spinal surgeries (procedures) (SSISp)

To designate SSISp, general terminology is used (see the "Terms and Definitions" section) taking into account additional chronometric gradations (Table 4) [17].

Table 4. Onset timing of surgical site infections in spine surgery

If spinal implants are present in the spinal SSI area, the condition is classified as implant-associated. A process localized above the muscle fascia is classified as "superficial spinal SSI", and below the muscle fascia as "deep spinal SSI".

1.6 Clinical presentation of the disease or condition

Leading complaints presented by patients with suspected inflammatory lesions of the spine:

- body temperature elevation above 38 °C;

- back pain — gradually developing, independent of position, poorly relieved by analgesics (severity assessed using VAS);

- neurological (motor and/or sensory) disorders and/or pelvic organ dysfunction — radicular pain syndrome, paresis, plegia;

- symptoms related to the level of the lesion: dysphagia for the cervical region, autonomic disorders for the thoracic region.

Anamnesis — history of infectious diseases, surgeries, procedures, contacts with infected individuals; presence of concomitant diseases, including primary or secondary immunodeficiency states (diabetes mellitus, viral hepatitis, HIV infection, rheumatoid arthritis, untreated focus of infection in another location).

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing the diagnosis/condition:

The diagnosis of an inflammatory spinal lesion is established based on a combination of clinical data, diagnostic imaging, and clinical and laboratory test results, including morphological, bacteriological, and molecular genetic analysis. However, the diagnosis of infectious spondylitis is considered definitely proven only with bacteriological confirmation (see Section 2.3).

2.1 Complaints and Anamnesis

2.2 Physical Examination

2.3 Laboratory Diagnostics

- microbiological (culture) blood test for sterility (for acute nonspecific spondylitis) [24];

- microbiological (culture) test for sterility of biopsy and surgical material — visualized and accessible substrate of the disease — abscess, infiltration zone, vertebral destruction zone, fistula, etc. [26].

GCR ALOE 2Grade of Recommendation A (Level of Evidence – 2)

Comments. It is optimal to perform blood cultures before starting antibiotic therapy at the peak of temperature rise (standard); however, due to low bacterial virulence, the result may be negative in 75% of patients. Blood culture analysis is particularly important in septic or critically ill patients [24]. If spinal infection is suspected in patients with negative blood cultures, it is advisable to perform a biopsy with morphological examination of the biopsy material [26]. Due to the low detection rate of pathogenic microflora during antibiotic therapy, in cases of exacerbation or chronic process, the biopsy is performed 1–2 weeks after stopping antibiotics.

Comments. Standards for examining purulent discharge for Mycobacterium tuberculosis include culture and polymerase chain reaction (PCR) methods, microbiological (culture) testing of bone tissue on liquid nutrient media for Mycobacterium tuberculosis complex, and microbiological (culture) testing to determine the drug susceptibility of Mycobacterium tuberculosis complex to first- and second-line antituberculosis drugs [27]. Granulation and necrotic tissue obtained from diagnostic or therapeutic procedures (biopsy, surgery) must also be examined. The rate of culture verification of MTC is 30–44%; DNA extraction and nucleotide sequence amplification increase it up to 89.7%.

Comments: sampling of contents for bacteriological examination is performed from the destruction focus, purulent cavities, destroyed vertebral bodies, and abscesses. The informativity of closed puncture (aspiration for liquid pus) or trephine biopsy reaches 41–90% (Level B) [24, 26].

Open biopsy, generally as part of a debridement surgery, is indicated for uninformative closed biopsies, inaccessible foci, destruction with compression of neural structures, and clinical signs of myelopathy. The material is examined using culture and molecular genetic methods (standard), including for aerobic and, where possible, anaerobic bacteria;

Performing a single course of antibacterial (including empirical) therapy reduces the likelihood of bacteriological confirmation of the diagnosis by more than half.

A morphological conclusion corresponding to an inflammatory process does not confirm an infectious lesion, except when etio-specific signs are identified (e.g., granulomas with Langhans giant cells and central necrosis in tuberculosis).

In immunodeficiency states, typical specific granulomas may be absent due to impairment of the phagocytic link of the immune response.

Comment. The diagnostic value of immunohistochemical methods for tuberculosis has not been proven. Immunological tests are used only to assess the activity of inflammatory and infectious diseases (option), but not to verify their etiology.

2.4 Instrumental Diagnostics

- spinal radiography, vertical (overview in 2 projections) — in all patients for a preliminary assessment of vertebral destruction and spinal deformity;

- computed tomography of the spine (one region) (CT) — in all patients to visualize the bone structures of the spine; CT myelography — to visualize the spinal canal if MRI cannot be performed; CT fistulography — when deciding on surgery and needing spatial visualization of the fistula and its connection with the vertebrae;

- magnetic resonance imaging of the spine (one region) (MRI) — in patients with neurological deficits to visualize the spinal canal, spinal cord, paravertebral tissues, and to detect inflammatory changes in the spine when CT findings are negative;

- radioisotope scanning (whole-body bone scintigraphy) and positron emission tomography (PET-CT) — when other imaging methods are insufficiently informative for detecting inflammation foci (primary and metastatic) and assessing their metabolic activity.

Level of evidence 1 (Level of certainty of evidence — C).

Comment: reliable radiopharmaceutical uptake (greater than 30%) in nonspecific spondylitis is detected in 2/3 of cases; an increasing uptake ratio over time may indicate disease progression.

Comments: In the absence of contraindications to the patient's verticalization, radiographs are performed in the standing position with maximum coverage of the spine.

Comment: The administration of gadolinium-based contrast agents from the V08CA group "Paramagnetic contrast media" is used to differentiate the inflammatory process from degenerative changes in the endplate and intervertebral disc. On T1-weighted images, gadolinium increases signal intensity around fluid collection areas; signal enhancement around low-density areas indicates abscess formation.

Comment: the first radiological and CT signs of spondylitis are detected no earlier than 2–4 weeks of the disease as foci of destruction with uneven and blurred contours;

An increase in the zone of bone destruction 4–6 weeks after the onset of the disease, provided that subjective complaints are relieved and laboratory parameters normalize during treatment, is not considered disease progression due to the "lag" of imaging data behind morphological repair processes;

The diagnostic significance of various diagnostic methods for non-specific spondylitis is presented in Table 5.

Table 5. Specificity and sensitivity of various diagnostic methods for inflammatory lesions of the spine

2.5 Other Procedures

• Patients with infectious spondylitis are recommended specialist consultations for diagnostic purposes [1, 5, 28]:

- neurologist consultation for all patients to identify complications of the disease;

- urologist consultation for all patients with pelvic organ dysfunction, renal failure, acute and chronic urinary tract infection;

- clinical pharmacologist consultation in case of antibiotic-resistant microflora detection; when prescribing more than 5 drugs; in the presence of sepsis.

GDR CLE 5Grade of recommendation C (level of evidence – 5)

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1 Conservative treatment of infectious spondylitis

Comments: Timely (early) conservative treatment allows for the relief of acute spondylitis in 56–75% of patients.

• Conservative treatment methods are recommended as the leading component of treatment in the following situations [28, 30, 31]:

- with limited vertebral destruction and no threat of complications;

- in acute processes and the absence of clinical signs of spinal cord compression and abscesses;

- in progressive and chronic spondylitis and severe comorbidities with a high risk of life-threatening complications from invasive procedures, including surgery, that outweighs potential efficacy.

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comment: a modular orthosis is used in the absence of spinal deformity, while a custom-molded orthosis fitted directly to the patient is used in the presence of spinal deformity.

3.1.1 Antibacterial therapy

Whenever possible, antibacterial therapy for inflammatory infectious diseases of the spine should be withheld until the results of bacteriological studies of biopsy material are obtained [40]. In case of sepsis or neurological disorders, immediate empirical antibacterial therapy is indicated [41]. If the bacterial pathogen is not identified in the culture of biopsy material or blood, but there are clinical and radiological signs indicating an infectious origin of the inflammatory spinal disease, it is advisable to prescribe empirical antibacterial therapy.

• Patients with inflammatory infectious diseases of the spine are recommended to be prescribed antibacterial therapy in accordance with the results of bacteriological studies of biopsy material and/or blood, taking into account the sensitivity of the identified bacterial pathogen to antibacterial drugs (determination of microorganism susceptibility to antimicrobial chemotherapeutic agents, rapid endotoxin susceptibility testing in purulent discharge, microbiological (culture) blood test for sterility) [42].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: For recommended antibacterial drugs according to the identified pathogens, see Appendix A3.1.

• Patients with inflammatory infectious diseases of the spine presenting with clinical and laboratory signs of sepsis, hemodynamic instability, or progressive neurological disorders are recommended to receive empirical antibacterial therapy without waiting for the results of bacteriological studies [40].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: Empirical antibacterial therapy must cover the entire spectrum of the most probable pathogens; therefore, it is advisable to prescribe combination antibacterial therapy including vancomycin** in combination with one of the following systemic antibacterial drugs (ATC J01): cefotaxime** (2 g IV every 6 h), ceftazidime** (1–2 g IV every 8–12 h), ceftriaxone** (2 g IV every 24 h) (third-generation cephalosporins), cefepime** (2 g IV every 12 h) (fourth-generation cephalosporins) or ciprofloxacin** (400 mg IV every 12 h or 500–750 mg orally twice a day) (fluoroquinolones).

If empirical therapy does not lead to objective clinical improvement (decrease in inflammatory markers, resolution of fever and back discomfort) within 3 to 4 weeks, a repeat percutaneous needle biopsy or open surgical biopsy is required to verify the pathogen.

• Antibacterial therapy for uncomplicated inflammatory infectious diseases of the spine is recommended to be continued for 6 weeks from the date of initiation of antibacterial therapy [42–44].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: A longer duration of treatment (in some cases up to eight weeks) is recommended for patients with undrained paraspinal abscesses and/or infections caused by drug-resistant microorganisms (including MRSA). In certain cases, up to 12 weeks of therapy may be required, especially with extensive bone involvement; the duration of treatment should be determined individually during clinical follow-up.

• The efficacy of ongoing antibacterial therapy should be assessed after 4 weeks of treatment based on the dynamics of systemic inflammatory response parameters—erythrocyte sedimentation rate and C-reactive protein level [40].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: Unchanged or elevated (compared to baseline) values of these parameters indicate the potential inefficacy of the ongoing antibacterial therapy.

3.1.2 Monitoring the efficacy of anti-tuberculosis chemotherapy

- to perform chemotherapy for tuberculous spondylitis to improve treatment outcomes in accordance with national clinical guidelines based on WHO recommendations and standards [30, 45];

- to conduct a main course of chemotherapy for spondylitis caused by susceptible and monoresistant strains of Mycobacterium tuberculosis for at least 12 months, and for multidrug-resistant strains for at least 18 months [28, 30, 45].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comment: Anti-tuberculosis chemotherapy (ATT) is initiated upon establishing the diagnosis of tuberculosis. The duration of preoperative ATT is determined by the time required to arrange the patient's transfer to a specialized department for bone and joint tuberculosis. In the postoperative period, ATT is continued at the anti-tuberculosis dispensary. The duration of the main course of ATT for tuberculous spondylitis depends on the drug susceptibility of the pathogen and is at least 12 months for drug-susceptible and monoresistant mycobacterial strains, and at least 18 months for multidrug-resistant strains.

3.2 Surgical Treatment

Comment: Indications for surgical treatment include:

- paravertebral abscesses, purulent tracts, incl. in a septic state in hemodynamically stable patients;

- ineffective antibacterial therapy with disease progression or persistence of clinical complaints;

- appearance/progression or persistence of neurological disorders in proven spinal cord compression by an epidural abscess, sequestra, etc.;

- chronic course of spondylitis accompanied by clinical complaints – back pain, fistulas, fever, progression of deformity, as well as laboratory activity.

Debridement of the focus is performed as an independent procedure or as a stage of reconstructive surgery, using open, minimally invasive, or endoscopic techniques [1, 5, 6, 36–39].

At the pre-destructive stage of spondylitis, visualized only on MRI by edema of the vertebral body cancellous bone, puncture (transpedicular biopsy) with local administration of antibacterial drugs can be performed as a therapeutic and diagnostic procedure [option].

- for anterior column reconstruction – autografts (iliac crest, ribs, tibia), allografts, and non-biological support implants;

- posterior instrumental fixation;

- a combination of methods.

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments. For posterior instrumental fixation, various options of support elements can be used – hooks, pedicle screws, hybrid (option).

- in infectious spondylitis with spinal instability, to perform laminectomy without subsequent stabilization;

- to perform surgical treatment of patients in an extremely grave somatic condition that is life-threatening to the patient [1, 5, 6], with the exception of minimally invasive debridement procedures.

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment: subcompensated somatic status: septic condition, except for purulent streaks and abscesses requiring emergency surgery; severe comorbidities and somatic conditions with a high risk of postoperative mortality (ASA class IV [Appendix G2]) are considered relative contraindications to surgery.

3.2.1. Principles of surgical treatment of surgical site infections associated with metal implants

• To improve the outcomes of treatment for implant-associated surgical site infections, it is recommended [1,5,6]:

- active sanitation of the surgical site, including VAC therapy if necessary;

- prolonged antibiotic therapy;

- preservation of stable implants to prevent spinal instability in early implant-associated surgical site infections (within the first 3 weeks from surgery);

- removal of implants in case of instability, followed by restabilization after inflammation resolution;

- removal of implants in late implant-associated surgical site infections (more than 90 days from surgery).

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: To prevent spinal instability in delayed implant-associated surgical site infections (from 3 weeks to 3 months from surgery), the decision to remove stable implants is made individually depending on the severity of inflammatory changes and the response to conservative treatment [1,5,6].

Repeat spinal instrumentation is performed only after complete resolution of the inflammatory process [1,5,6].

Comments: bacteriological study for low-pathogenic flora, including preliminary treatment of removed implants with ultrasound (sonication) for the potential destruction of biofilms in late implant-associated surgical site infections accompanied by peri-implant resorption or a mild inflammatory response—intermittent low-grade fever, moderate elevation of ESR or CRP levels.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Rehabilitation treatment is recommended for all patients with inflammatory spinal lesions during both conservative and surgical treatment; it should begin after the relief of intoxication in conservative treatment and in the early postoperative period, and be carried out under the supervision of a physical and rehabilitation medicine (PRM) physician. In cases of infectious spondylitis complicated by neurological disorders, rehabilitation should be carried out under the supervision of a PRM physician and a neurologist, with consultation by a urologist as indicated, including after discharge from the hospital [46, 52, 56].

Despite the different etiology of inflammatory spinal diseases (purulent, bacterial, specific, hematogenous), in all cases the stages of rehabilitation will be of the same type, with differences in the timing of onset and duration of each stage. There are no standardized rehabilitation protocols with proven efficacy, and very few studies address rehabilitation in spinal infections [46,47, 52, 56].

However, it has been noted that rehabilitation should help patients return to their daily lives by ensuring early mobilization with pain reduction, strengthening weakened muscles, stabilizing the spine, and maintaining proper posture [47, 48, 50, 60].

Comments: The MDRT includes a PRM physician, a physical therapy instructor-methodologist, a medical psychologist, in some cases an occupational therapist (ergotherapist), and a medical rehabilitation nurse. The team must coordinate rehabilitation tactics, set a common patient rehabilitation goal, and draw up protocols (programs).

Comments: In the acute phase of the inflammatory process, bed rest is prescribed, and, after consultation with a PRM/exercise therapy physician and in the absence of contraindications, an individual rehabilitation program is drawn up in accordance with the severity of the patient's general condition, comorbid diseases, localization of inflammation, and clinical symptoms. Considering the mechanisms of action of rehabilitation agents and methods, the following are prescribed: [49, 50, 59]

- therapeutic exercise for spinal disorders (dynamic exercises for the upper and lower extremities, isometric exercises for the gluteal muscles, back muscles, and abdominal press);

- breathing exercises;

- TENS (A17.24.001 Percutaneous electrical nerve stimulation in diseases of the peripheral nervous system);

- mobilization within the bed and preparation for verticalization.

Comments: upon normalization of inflammatory markers, the patient is verticalized in a plaster or rigid corset and discharged from the hospital for outpatient follow-up. External immobilization with a corset or rigid orthosis is mandatory in the treatment of infectious spondylitis accompanied by spinal instability and pain syndrome. In the absence of spinal deformity, removable modular orthoses can be used, whereas in the presence of spinal deformity, orthoses are custom-made with direct molding to the patient [47].

The PRM/exercise therapy physician draws up an individual rehabilitation program prescribing [5,8,9,12,16]:

- orthopedic regimen;

- therapeutic exercise for spinal disorders (dynamic general tonic exercises for the upper and lower extremities, isometric exercises for the back and abdominal muscles, training on horizontal stationary bikes, exercises on pulley weight machines for the arms);

- breathing exercises;

- balance training (balance therapy);

- graded walking, if necessary with assistive devices.

Follow-up consultations with the PRM/exercise therapy physician are carried out at intervals of 2–3 weeks throughout the entire period, the duration of which ranges from 3 to 6 months. Follow-up consultations and adjustment of prescriptions make it possible to monitor the state of the musculoskeletal system and problems associated with prolonged immobilization [50].

Comments: the consequences of the inflammatory process in the spinal structures and prolonged corset wear of up to 6 months or more lead to impaired spinal shape and function and corresponding muscle groups. Therefore, this stage of rehabilitation is necessary under the supervision of a PRM/exercise therapy physician, who draws up an individual program prescribing [46-48, 54, 57, 59]:

- static and dynamic exercises with weights for spinal stabilizer muscles;

- exercises in water (pool-based exercise therapy) and therapeutic swimming in the pool;

- equilibrium and balance training with biofeedback (exercise therapy with biofeedback for spinal disorders);

- corrective exercises (as indicated);

- gait training;

- medical back massage / hydrokinesiotherapy for spinal disorders;

- physiotherapy (ultrasound therapy for peripheral nervous system diseases, interference current therapy, sinusoidal modulated current therapy, transcutaneous electrical nerve stimulation [TENS]).

Physiotherapy and rehabilitation have an important impact on pain relief and the restoration of spinal function, accelerating the adaptation to daily activities and return to work [50, 57, 60].

Timely (early) rehabilitation treatment allows for faster relief of pain symptoms, mobilization of the patient, and their adaptation to daily and occupational activities [46, 49, 56].

Comments: from the first day after surgery, in the absence of contraindications, the PRM/exercise therapy physician draws up an individual rehabilitation program prescribing: [53-55, 59]

- active dynamic exercises for the upper and lower extremities;

- breathing exercises;

- isometric exercises for the trunk muscles;

- local cryotherapy;

- electroanalgesia, TENS (A17.24.001 Percutaneous electrical nerve stimulation in diseases of the peripheral nervous system);

- low-level laser skin irradiation;

- training in activities within the ward regimen;

- preparation for verticalization.

Rehabilitation programs for patients with neurological deficits include passive exercises, active-assisted exercises, positioning therapy, orthopedic stacking, and muscle electrical stimulation.

When drawing up the rehabilitation program and indications for orthotic management (the need for corset or brace immobilization) in the postoperative period, it is recommended to take into account the presence of instability in the spinal segment, localization of the lesion, type of surgical intervention, stage of the inflammatory process, and the patient's general condition and age [51].

Following verticalization, walking with assistive devices is taught, and the patient is discharged home under outpatient follow-up.

Comments: it is necessary to target the spine in order to preserve its function, stimulate metabolic processes, improve blood circulation, strengthen the muscular corset, and mobilize the patient [51, 53-55, 58, 59].

In the absence of contraindications, the PRM/exercise therapy physician draws up an individual rehabilitation program prescribing:

- therapeutic exercise for spinal disorders;

- biofeedback training based on support reaction and podographic parameters;

- medical back massage;

- back muscle electrical stimulation;

- ultrasound therapy for peripheral nervous system diseases;

- exercises in water (pool-based exercise therapy) and therapeutic swimming in the pool;

- gait training.

Rehabilitation modalities are used with individually selected, correct dosages, taking into account individual contraindications, the specifics of the surgical intervention, and clinical symptoms.

Corset wear continues for 3 months until the first radiological signs of bone fusion appear [60].

Rehabilitation courses are repeated throughout the entire recovery period, which lasts approximately 6 months.

Timely (early) rehabilitation treatment allows for faster relief of pain symptoms, mobilization of the patient, and their adaptation to daily and occupational activities [46, 49, 56].

Comments: The treatment of inflammatory spinal diseases is prolonged and accompanied by sleep disturbances, mood changes, depression, and a decline in quality of life, which affects the patient's psychological state [64-66] and must be taken into account when drawing up rehabilitation programs.

5. Prevention and Dispensary Observation

• To prevent infectious lesions of the spine, it is recommended that all patients undergo sanitation of acute and chronic foci of infection in the body, promote a healthy lifestyle and preventive measures for infectious diseases, with a special focus on risk groups: patients with chronic metabolic diseases, including those receiving immunosuppressive therapy; and patients with primary and secondary immunodeficiency states [2, 5].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment: During the first 6 months, patients are evaluated by an orthopedic trauma surgeon and a neurologist once every 2 months. In the absence of clinical, radiological, and laboratory signs of exacerbation or complications, spinal radiography is performed 3 months and CT 6 months after the start of treatment. By 6 months, recovery or the transition of the disease to a chronic course is established. Follow-up MRIs are performed in patients with neurological disorders, as well as when clinical and laboratory activity of the inflammatory process persists in the absence of CT signs of progressive destruction [2, 5].

The criterion for effective treatment is the absence of clinical and laboratory manifestations of the disease. Radiological signs of osteorepair during conservative treatment—bone restoration, osteosclerosis, and vertebral fusion—appear 4 to 6 months after the start of treatment.

For patients who underwent surgical treatment, radiological signs of efficacy are the absence of progressive destruction, increasing spinal deformity, stable position of metal implants, absence of peri-implant resorption, and the presence of signs of fusion of bone structures—vertebrae and grafts.

• In the presence of complications, it is recommended to continue follow-up and treatment with specialized professionals to improve treatment outcomes [2, 5].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment: Follow-up is continued:

- by a surgeon, orthopedic trauma surgeon, or neurosurgeon in the presence of fistulas, instability, and spinal deformity. If these complications can be resolved, surgical treatment is performed in specialized spinal surgery departments/centers with the patient's consent and informing them of the corresponding surgical risks;

- by a neurologist, urologist, or physical and rehabilitation medicine physician in the case of myelopathy/radiculopathy;

- by a surgeon, plastic surgeon, or social workers in the case of irreversible neurological and neurotrophic disorders.

• To comply with the national clinical guidelines of the associations of phthisiatricians and orders of the Russian Ministry of Health, it is recommended that patients with spinal tuberculosis be followed up within the dispensary registration groups of anti-tuberculosis institutions: group 1 – active tuberculosis; group 2 – chronic tuberculosis; group 3 – sequelae and residual effects of spinal tuberculosis [35].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments. Frequency of examination by an orthopedic trauma surgeon: once every 3 months during the first year after surgery [35].

6. Organization of Medical Care

Medical care for patients with infectious spondylitis is provided within the framework of specialized medical care in inpatient and outpatient settings. Depending on the severity of clinical manifestations, conservative treatment can be carried out in a surgical (or neurosurgical) or therapeutic (including neurological) inpatient department, and its continuation can be inpatient or outpatient.

Indications for hospitalization are:

1. Clinical manifestations of acute infectious spinal disease.

2. Neurological complications of infectious spondylitis.

3. Vertebrogenic pain syndrome refractory to conservative methods in subacute and chronic spondylitis;

4. Spinal instability secondary to vertebral destruction, including that accompanied by pain syndrome and spinal deformity, impairing the patient's quality of life;

5. Chronically functioning fistula (more than 3 months).

Indications for discharging a patient from an inpatient medical facility are:

1. When hospitalized for acute infectious spondylitis:

   - relief of clinical signs of the acute inflammatory process;

   - normalization of laboratory parameters – ESR, CRP, leukocyte formula;

   - absence of signs of infectious and inflammatory changes in the surgical intervention area;

   - relief of vertebrogenic pain syndrome to levels that do not require injectable painkillers or are subjectively rated by the patient as no higher than 3 points on the VAS.

2. In subacute or chronic spondylitis – achievement of positive dynamics regarding the clinical symptoms that served as the reason for hospitalization.

Further treatment of the patient upon relief or improvement of the clinical manifestations of infectious spondylitis can be continued on an inpatient or outpatient basis, including in specialized hospital departments—urology, neurology, and rehabilitation departments/centers; for patients with tuberculous spondylitis, in an anti-tuberculosis dispensary under the supervision of a surgeon and/or orthopedic trauma surgeon.

Surgical treatment of patients with spinal tuberculosis is performed in specialized departments of federal research institutes and anti-tuberculosis dispensary hospitals. In cases of acute (up to 48 hours) paraplegia in a patient with spinal tuberculosis, emergency surgical treatment is performed in any neurosurgical department.

7. Additional Information

7.1. Factors negatively affecting treatment outcomes:

1. Factors characterizing patient features:

- concomitant acute and chronic non-inflammatory comorbidities – diabetes mellitus, obesity, oncological diseases;

- concomitant chronic inflammatory diseases of the urinary and respiratory systems, oral cavity, skin, and subcutaneous adipose tissue; diseases accompanied by neurotrophic disorders;

- smoking, alcoholism;

- immunodeficiency states, including those caused by prior therapy (glucocorticoids, immunosuppression); primary immunocompromised states; co-infection (HIV infection).

2. Factors characterizing disease features:

- drug resistance of the pathogen;

- septic course of the disease;

- neurological complications of the process, primarily structural changes in the spinal cord (irreversible MRI manifestations of myelopathy)

3. Factors associated with disease treatment:

- irrational, including empirical, antibacterial therapy;

- development of severe adverse events (systemic complications) of antibacterial therapy;

- non-radical debridement of the purulent focus;

- unstable instrumental fixation.

Quality of life assessment is performed using the Oswestry disability index (Appendix G3).

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

¹ - Russian Association of Spine Surgeons (RASS); ² – Association of Traumatologists and Orthopedics of Russia (ATOR); ³ - Association of Neurosurgeons of Russia (ANR); ⁴ - AO Spine; ⁵ – Russian Association of Phthisiatricians, RAP; ⁶ – National Association of Phthisiatricians, NAP, ⁷ – All-Russian Union of Rehabilitologists,

Conflict of interest:

The authors declare no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Trauma and orthopedic surgeons

2. Surgeons

3. Neurosurgeons

4. Phthisiatricians

5. Infectious disease specialists

Table 1. Level of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)

Table 2. Scale for evaluating the levels of evidence (LE) for prevention, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for evaluating the levels of recommendation certainty (LRC) for prevention, diagnostic, treatment, and medical rehabilitation methods, including those based on natural healing factors (preventive, diagnostic, therapeutic, and rehabilitation interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years. If new evidence-based data regarding the diagnosis, treatment, prevention, and rehabilitation of specific conditions emerge, or if justified additions/comments to previously approved clinical guidelines become available, updates may be made on a case-by-case basis, but no more than once every 6 months.

Appendix A3. Reference Materials

Appendix A3.1. Antibacterial drugs for the treatment of major bacterial pathogens of inflammatory spinal infections based on susceptibility, classified under soft tissue infections and bone and joint infections [67]

The choice of systemic antibacterial drugs and dosage regimens is presented in accordance with the primary source [67].

¹ it is advisable to monitor trough serum concentrations of vancomycin**

Appendix B. Physician Action Algorithms

1. Physician action algorithm for suspected acute inflammatory spinal disease (emergency interventions are highlighted in bold italics)

2. Physician action algorithm for surgical site infection in a patient with a history of spinal surgery.

Appendix C. Patient Information

If complaining of back pain accompanied by malaise and fever, the patient should consult a surgeon or traumatologist-orthopedist.

If complaining of back pain accompanied by malaise, fever, limb weakness, urinary and/or fecal incontinence, the patient should immediately consult a surgeon, traumatologist-orthopedist, neurologist, or neurosurgeon.

A patient treated in a hospital for infectious spondylitis must, upon discharge, contact the local outpatient clinic to register for follow-up care with a surgeon or traumatologist-orthopedist.

Patients with persistent motor deficits after treatment should be monitored by a neurologist, and those with urinary symptoms or urinary tract infections by a urologist.

Following spinal osteomyelitis, patients should avoid sports involving vertical spinal loads for 6 months. The possibility of returning to normal social and physical activity is discussed with the attending physician, taking into account follow-up clinical and imaging findings.

If signs of inflammation develop in the area of spinal surgery, the patient should consult the surgical center where the operation was performed.

A patient operated on for tuberculous spondylitis who was not previously registered with the anti-tuberculosis dispensary (ATD) must apply for registration at the local ATD upon discharge from the hospital.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Frankel Neurological Scale

Source (official developer website, validated publication): Frankel H.L. The value of postural reduction in the initial management of closed injuries of the spine with paraplegia and tetraplegia / H.L. Frankel, D.O. Hancock, G. Hyslop, J. Melzak, L.S. Michaelis, G.H. Ungar, J.D. Vernon, J.J. Walsh // Paraplegia. – 1969. – Vol. 3, № 7. – P. 179–192.

Type (underline): rating scale

Purpose: Assessment of the neurological status of patients

Content (template):

Key (interpretation): a higher functional class corresponds to a more favorable neurological status of the patient.

Appendix G2. General Somatic Status Scale

Original title (if applicable): ASA Physical Status Classification System

Source (official developer website, validated publication): www.asahq.org/standards-and-guidelines/asa-physical-status-classification-system

Type (underline): rating scale

Purpose: Assessment of patients' functional status

Content (template):

* E – emergency procedure

Key (interpretation): a higher score corresponds to a lower functional status.

Appendix G3. Oswestry Disability Index

Original title (if applicable): Oswestry Disability Index

Source (official developer website, validated publication): Fairbank J.C., Pynsent P.B. The Oswestry Disability Index // Spine (Phila Pa 1976). 2000 Nov 15;25(22):2940-52

Type (underline): rating scale

Purpose: Assessment of quality of life

Content (template):

Key (interpretation): the total score is evaluated according to the source. A higher score corresponds to a lower quality of life.

Appendix G4. Visual Analog Scale for Pain (numerical)

Original title (if available): Visual analog scale

Source (official developer website, validation publication): Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res (Hoboken). 2011; 63 Suppl 11: S 240–252

Type (underline): rating scale

Purpose: Assessment of pain severity

Content (template):

Key (interpretation): 0 — no pain, 10 — worst possible pain.