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ESPID Clinical Practice Guideline

Bone and Joint Infections

Saavedra-Lozano, Jesús MD, PhD*†; Falup-Pecurariu, Oana MD, PhD‡; Faust, Saul N. MB BS, MRCPCH, PhD§; Girschick, Hermann MD¶‖; Hartwig, Nico MD, PhD**; Kaplan, Sheldon MD††‡‡; Lorrot, Mathie MD, PhD§§; Mantadakis, Elpis MD¶¶; Peltola, Heikki MD, DTM& H‖‖; Rojo, Pablo MD, PhD***; Zaoutis, Theoklis MD, MSCE†††; LeMair, Anton MD‡‡‡

Author Information

From the *Complutense University of Madrid, and †Department of Pediatrics, Infectious Disease Unit, Gregorio Marañón Hospital, Madrid, Spain; ‡Department of Pediatrics, Children’s Clinic Hospital, Faculty of Medicine, Transilvania University, Brasov, Romania; §NIHR Wellcome Trust Clinical Research Facility, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; Vivantes Klinikum im Friedrichshain, and ‖Department of Pediatrics, Clinic for Pediatric and Adolescent Medicine, Berlin, Germany; **Department of Pediatrics, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands; ††Baylor College of Medicine, and ‡‡Department of Pediatrics, Infectious Diseases Service, Texas Children’s Hospital, Houston, Texas; §§Équipe opérationnelle d’infectiologie et service de pédiatrie générale, Hôpital Armand Trousseau, Université Pierre et Marie Curie, Paris, France; ¶¶Department of Pediatrics, Democritus University of Thrace Faculty of Medicine, University General Hospital of Evros, Alexandroupolis, Thrace, Greece; ‖‖Children’s Hospital, University of Helsinki, Helsinki, Finland; ***Department of Pediatrics, Pediatric Infectious Diseases Unit, Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain; †††The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; and ‡‡‡ALM Consulting, The Netherlands.

Accepted for publication May 8, 2017.

For funding and disclosure statement, refer Supplemental Digital Content, https://links.lww.com/INF/C729.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com).

Address for correspondence: Jesús Saavedra-Lozano, MD, PhD, Servicio de Pediatría, Sección Enfermedades Infecciosas, Hospital Materno-Infantil Gregorio Marañón, C/O’Donnell 48-50, 28009 Madrid, Spain. E-mail: [email protected].

The Pediatric Infectious Disease Journal 36(8):p 788-799, August 2017. | DOI: 10.1097/INF.0000000000001635

1. INTRODUCTION

The European Society for Paediatric Infectious Diseases (ESPID) Bone and Joint Infection Guidelines (ESPID Guidelines) are intended for use by health providers who take care of children with bone and joint infection (BJI). Although BJI can include a diverse range of presentations, these guidelines will focus on “acute, hematogenous BJI in children,” with an emphasis on bacterial infections.

ESPID Guidelines are consensus-based practice recommendations developed in a systematic manner that aim to be clear, valid and reliable, and presented with clinical applicability. Because evidence from large randomized controlled trials is rare or lacking, practice statements and recommendations provided here frequently reflect our expert consensus process based on best current practice.

Although these guidelines include evidence-based and opinion-based recommendations for the diagnosis and management of children with BJI, these guidelines may not provide the best clinical solution and are not intended to serve as a substitute for the clinical judgment of physicians in individual cases or to establish a protocol valid for all children with these infections. Consequently, they do not represent the “only” appropriate approach for children with this kind of infection.

We kindly refer to the full version available online (Supplemental Digital Content, https://links.lww.com/INF/C729) for more information on sources used, literature search strategies, guideline development methodology and the ESPID Review Team.

The authors of these ESPID Guidelines have made considerable efforts to ensure that the information upon which they are based is accurate and up-to-date. Users of these guidelines are strongly recommended to confirm that the information contained within them, especially drug doses, is correct by way of independent sources. ESPID and the authors of these guidelines accept no responsibility for any inaccuracies, information perceived as misleading or the outcome of any treatment regimen detailed in the guidelines.

2. SUMMARY OF BJI RECOMMENDATIONS

There is a paucity of clinical trial or prospective cohort study data to inform the diagnosis and management of BJI in children. Most data are derived from retrospective, observational studies of variable quality. Therefore, ESPID decided to apply a simple grading of the practice statements in this guideline (see notes below).

  1. BJI more frequently affects children younger than 5 years of age, and the infection more often involves joints and bones of the lower extremities (IIA).
  2. Staphylococcus aureus is the most prevalent microorganism involved in BJI in children at all ages. In addition, Kingella kingae is a common causative pathogen in children <5 years old in some regions (IIA).
  3. C-reactive protein (CRP) and erythrocyte sedimentation rate for the diagnosis of BJI have a high sensitivity, which is slightly increased by combining the 2 tests, whereas the specificity is low (IIB).
  4. Ultrasound (US) has a high sensitivity for the diagnosis of septic arthritis (SA), whereas magnetic resonance imaging (MRI) is the most reliable imaging study for the diagnosis of BJI overall (IIA).
  5. The isolation of a microorganism from the bone, joint or blood with a clinical or radiologic syndrome compatible with BJI is the gold standard for diagnosis in children (IIA).
  6. Empirical antibiotic therapy should be started as soon as possible after collecting appropriate samples for microbiologic analysis upon suspecting BJI in children (IIA).
  7. Empirical therapy should include an antibiotic with appropriate coverage against methicillin-sensitive S. aureus (MSSA) and against methicillin-resistant S. aureus (MRSA) in geographical areas with more than 10%–15% prevalence of this bacterium (IIA).
  8. Empirical therapy in young children needs to include appropriate coverage for K. kingae in relevant areas (IIA).
  9. First-generation cephalosporins, anti-staphylococcal penicillins (ASPs) and clindamycin are the antibiotics most studied in BJI in children (IIA).
  10. If MRSA infection is suspected and the patient is not critically ill, empirical therapy should include clindamycin if the rate of clindamycin-resistant S. aureus is less than 10%–15%. A glycopeptide or other appropriate antibiotic for MRSA, such as linezolid, should be included if local clindamycin-resistant MRSA rates are high (IIIB).
  11. SA in children should be treated with joint drainage by arthrocentesis, arthrotomy or arthroscopy, depending on the preference and experience of the treating clinicians and surgeons. Arthrocentesis may be appropriate as the only invasive procedure in most uncomplicated cases of SA in children (IIB).
  12. Short intravenous (IV) therapy followed by oral therapy is appropriate in the majority of children with uncomplicated BJI based on absence of complications and favorable outcome (IA).
  13. Follow-up oral antibiotic therapy should be guided by the antibiotic susceptibilities of the bacteria if isolated; if susceptible, the antibiotics of choice are first-generation cephalosporins and clindamycin (IIA).
  14. The minimum total duration of antibiotic therapy should be 2–3 weeks for SA and 3–4 weeks for osteomyelitis (OM) (IA).
  15. Complicated or high-risk BJI such as those produced by Salmonella, MRSA or Panton–Valentine leukocidin (PVL)-positive strains, developing in young infants, or with slow clinical improvement, may need to receive longer duration of both IV and oral therapy (IIB).
  16. Risk factors associated with sequelae include young infants and newborns, infections caused by MRSA or PVL-positive strains, longer duration of symptoms before initiation of therapy and hip involvement. Thus, children with BJI who have any of these risk factors should be followed more closely and for a longer time to rule out or treat sequelae (IIB).
  17. A multidisciplinary team should follow children with BJI until osteoarticular function is restored and sequelae are resolved. If bone growth is the only concern, an orthopedic specialist will suffice. Infants with BJI in hip or with any physis involvement should be followed for extended periods of time (IIB).

Notes

  • – Quality of evidence
    • I = Good evidence: Randomized placebo controlled trials; other studies appropriately randomized; good meta-analysis and systematic reviews of randomized controlled trials.
    • II = Moderate evidence: Well designed but not randomized studies, cohort and case control studies.
    • III = Poor evidence: Expert opinion, case series.
  • – Strength of recommendation—team consensus based on calculation of votes for A, B or C by the team members: A = strong recommendation; B = moderate recommendation and C = weak recommendation.

3. EPIDEMIOLOGY

Musculoskeletal infections involve bones, muscles and joints and are a significant cause of morbidity, and mortality in certain circumstances or settings, in children worldwide.1,2 Acute hematogenous BJI in children may clinically manifest as OM, SA, both combined (OM-SA) or pyomyositis. Pediatric spondylodiscitis is uncommon and accounts for 1%–2% of all children with OM. Pyomyositis may complicate BJI and can also be a primary infection without the coexistence of BJI.

  • Acute OM is an inflammatory process in the bone with bone destruction usually resulting from bacterial infection.3 In high-income settings, the time from onset of symptoms to presentation for medical care is usually <5 days, and rarely more than a week.4,5 Half of the children with acute hematogenous OM are under 5 years of age.1
  • SA is an acute infection of the joint that occurs most commonly in young children, mainly monoarticular.4,6 (See Section 5 “Clinical Features.”)
  • Spondylodiscitis is characterized by infection involving the intervertebral disc and adjacent vertebrae. Early in the disease, differentiation between discitis and vertebral OM may be difficult. The pathogens implicated in discitis are similar to those in other BJI.3 It occurs mainly in children <5 years of age.2,7 Vertebral OM is more common in older children and usually involves the anterior vertebral body.7 In these instances, infectious agents such as Mycobacterium tuberculosis and Salmonella should be considered.
  • Pyomyositis is frequently seen with pelvic involvement and may be related to MRSA or PVL production.8–11

3.1. European Guidelines

Europe is a group of countries with great differences in population, culture, wealth and health services. All variations of disease are impacted by differing epidemiology of pathogens and bacterial resistance, differences in presentation of reported cohorts between regions, medical approaches of infectious diseases, possibilities of medical care, etc.

To deal with variations in resource availability, this document aims to provide choices of diagnostic tools and options for treatment. Perhaps, see Table 3 in the full, online version (Supplemental Digital Content, https://links.lww.com/INF/C729) for BJI incidence in several European countries (between 1.4 and 22 per 100,000 people). Differences in incidence may also be related to dissimilar capacity to reach etiologic diagnoses and surveillance methods.

3.2. Predispositions/Risk Factors

Most BJI do not have a predisposed condition and occur in primarily healthy children. In specific situations, the following associations have been described.

  • Upper respiratory infection (K. kingae)12,13
  • Preceding trauma,14 although some recent papers question this since trauma is very common in children15
  • Wounds,3 erosions and varicella infection (group A Streptococcus)3
  • Sickle cell disease (Salmonella spp.)3,16
  • Immunodeficiency—for example, chronic granulomatous disease (Serratia and Aspergillus)17
  • Penetrating wounds—for example, through the sole of a shoe or sandal (anaerobes and Pseudomonas)2
  • Living conditions, occupation—for example, animal handling and laboratory work in cases of infection caused by Brucella and Coxiella spp.18,19
  • Contact with pulmonary tuberculosis or living in endemic areas (tuberculosis BJI)
  • Newborns: prematurity, skin infections, bacteremia or candidemia and previous central venous catheter20,21

4. ETIOLOGY AND PATHOGENESIS

  • Most BJI in children are of a hematogenous origin, and it is the focus of these guidelines. Much less frequently than in adults, BJI in children can be secondary to an adjacent infection, prosthetic material or traumatism.
  • For practical reasons, “acute” and “subacute” are usually considered those BJI with a history of <2 weeks and 2 weeks to 3 months, respectively.

4.1. Causative Agents and Bacterial Resistance

  • The prevalence of different pathogens encountered in various European countries is the main factor influencing the antibiotic regimen in BJI (Table 14, Supplemental Digital Content, https://links.lww.com/INF/C729). Some important points are a higher incidence of community-acquired MRSA (CA-MRSA) in some countries such as Romania or Greece, or important differences in K. kingae incidence within some countries (ie, very low in Scandinavia and quite high in Spain, France or United Kingdom). A recent European pediatric study of invasive S. aureus disease has shown a prevalence of 8% of MRSA.22

Table 1 illustrates the most common pathogens by age in acute BJI.

T1
TABLE 1.:
Most Common Pathogens by Age in Acute BJI3,4,16,23
  • OM and SA are most commonly caused by S. aureus, followed by K. kingae or group A Streptococcus depending on age and other risk factors, or geographical location. In some studies, K. kingae is the second (or even the first) most common etiology after S. aureus in children <5 years of age where real-time polymerase chain reaction (PCR) has been performed.5,24–27
  • Pathogens involved less frequently in these infections are Streptococcus pneumoniae, Pseudomonas, Salmonella, Haemophilus influenzae type b (Hib), among others.
  • Group B Streptococcus and Escherichia coli are important pathogens in newborns.
  • In certain areas, a variable but considerable number of cases are caused by CA-MRSA.

5. CLINICAL FEATURES

The “classical presentation” of BJI is fever, localizing signs of swelling or pain and limitation of movement or limping. Table 2 shows a summary of the most frequent signs and symptoms of children with BJI.

T2
TABLE 2.:
Clinical Features of BJI by Age and Location

5.1. General Symptoms

There is considerable overlap in the symptoms of OM, SA and pyomyositis: OM frequently has a more insidious onset; SA presents more frequently with fever, swelling and decreased range of motion, except when in occult joints, such as sacroiliac or vertebra; and pyomyositis of the psoas may also be very difficult to diagnose. Other symptoms are as follows:

  • Limping or non-weight bearing
  • Refusal to use limb and/or decreased range of motion6
  • Acute or subacute onset of complaints: SA 2–4 days5,29 and OM 6–7 days5,29
  • Fever is present in 30%–40% of cases.1,5,6,30
  • In newborns and young infants only nonspecific symptoms

A 2012 systematic literature review30 of pediatric studies of OM showed:

  • 81% pain
  • 70% localized signs and symptoms
  • 62% fever
  • 50% reduced range of motion
  • 50% reduced weight bearing.

5.2. Location-specific Symptoms

In children with BJI, the infection can affect any bone, muscle or joint. Most commonly the long bones and joints of the lower limbs are involved4–6 (Table 3). Multifocal OM is seen in 5%–10% of infants (especially newborns and young infants).6,31 Pain in OM tends to be more localized. Tenderness, redness and swelling are more common in SA. Pyomyositis, when it involves muscles around the hip joint, can mimic SA.32

T3
TABLE 3.:
Skeletal Distribution of BJI in Children1,2,6,16

6. DIAGNOSIS

See Table 4 for a summary of recommendations for the diagnosis of pediatric BJI.

T4
TABLE 4.:
Diagnostic Options for Childhood BJI

6.1. Laboratory Tests

In case of suspected BJI, the following tests are normally recommended: complete blood count, CRP and erythrocyte sedimentation rate.

At this time, there lacks clear evidence of the clinical benefit of procalcitonin.39–41 Gram staining can be very informative, both for synovial fluid and the potentially obtained bone aspirate/biopsy. This test is especially important because the culture may be negative. Synovial fluid cytology is not considered mandatory because its findings overlap with other diseases.

6.2. Microbiology

Blood culture with appropriate volume should always be performed before antibiotics.

Use of blood culture vials for culturing synovial fluid and bone exudates in recent years has resulted in the recognition of K. kingae as one of the most common causes of BJI in children <5 years of age in selected regions or countries.45

In recent years, nucleic acid amplification methods (eg, conventional and real-time PCR) have also improved the detection of bacteria not isolated by culture.25,45 This may be very important when prior use of antibiotics (synovial fluid PCR remains diagnostic up to 6 days after antibiotic initiation) or for a pathogen in which conventional diagnostic methods remain suboptimal.12,13,24–26,45K. kingae is identified mainly via eubacterial PCR using ribosomal RNA primers targeting the 16S ribosomal RNA gene. More specific primers may increase the sensitivity of PCR to detect Kingella.12,13,24

An etiologic diagnosis is highly recommended even though S. aureus is so common that an empirical anti MSSA/MRSA treatment would usually perform well, especially for children ≥5 years of age. Although most culture-negative cases of BJI can be successfully treated with empirical antibiotics, it is important to establish a microbiologic diagnosis to adjust therapy and to rule out noninfectious causes of the disease.

Whereas arthrocentesis has a therapeutic aim in SA (see “Section 7.5”), the need for a bone aspiration for a suspected uncomplicated OM is more controversial because this procedure does not seem to affect the outcome of these infections.4,23

See Table 4 for a summary of microbiologic approach to BJI.

6.3. Imaging Studies

Radiograph Imaging Radiograph imaging is considered an important baseline test in all patients for comparison of subsequent change if disease does not rapidly improve and to rule out other underlying conditions. See Table 4 for a summary of diagnostic procedures.

  • Acute OM: Frequently normal at baseline. Repeat imaging shows appearance of osteolytic changes or periosteal elevation, mostly 10–21 days after onset of symptoms.3
  • Subacute OM: Changes frequently seen can be confused with malignancies,46 which usually require operative biopsy for definitive diagnosis.
  • SA: Limited usefulness; soft tissue swelling
  • Discitis: Lateral spine radiographs show late changes at 2–3 weeks into illness, especially decreased intervertebral space and/or erosion of the vertebral plate.
  • Vertebral OM: Initially shows localized rarefication (thinning) of a single vertebral body, then anterior bone destruction. MRI may be indicated in suspected spondylodiscitis and vertebral or pelvic OM.

MRI MRI is the most informative imaging modality for OM, because it can detect abnormalities within 3–5 days of disease onset. Moreover, it reveals details of the bone and soft tissue involvement, including the formation of abscesses, sequestra or associated pyomyositis or contiguous venous thrombosis, and can help the orthopedic surgeon to plan the most appropriate surgery for diagnostic and/or therapeutic purposes. MRI may not be necessary in certain situations where other clinical and diagnostic tools are strongly suggestive of the diagnosis. It may be indicated in severe clinical conditions, there are reasonable doubts about the diagnosis, or when a complication is suspected. Other indications may be as follows:

  • SA: Although not generally indicated, it may be valuable if OM-SA is suspected. Thus, in a recent study,42 35% of children with acute OM had a contiguous SA.
  • Spondylodiscitis and vertebral OM: MRI may be a necessary test if these infections are suspected for detailing bone and soft tissue involvement and to rule out epidural abscess and tumor.
  • Pyomyositis: High sensitivity and specificity, especially useful for the hip and pelvis.

MRI disadvantages may be as follows: long scan times, need of sedation or anesthesia in young children and is a contraindication with some metallic foreign bodies and certain types of implanted hardware.38

Computerized Tomography Computerized tomography is not generally recommended: it is less sensitive compared with MRI in detecting early osseous lesions and exposes children to high radiation doses.43 It may be performed in settings where MRI is not feasible.

  • Valuable for guided procedures, such as aspiration or drainage,42 and may not need sedation because of the short time needed.

Sonography Sonography or US is most indicated for SA because it has a high sensitivity for the diagnosis of joint effusion, although with a lower specificity. It should be performed in all suspected SA unless easily diagnosed by physical examination. US may be useful for OM, mainly in the diagnosis of abscess formation and surrounding soft tissue abnormalities (pyomyositis, cellulitis, etc.), and it may provide guidance for diagnostic or therapeutic aspiration and/or drainage. Doppler US may provide early detection of a high vascular flow in the infected bone.37

Bone Scintigraphy or Bone Scan Technetium radionuclide scan (99mTc) is used to identify multifocal osseous involvement and to document the site of OM when local skeletal symptoms are ill defined.47 It has a high sensitivity but less specificity,48 and both are lower in neonates. It may also give false negative results in infancy and with virulent pathogens (MRSA).49 SPET-CT may increase the sensitivity of bone scintigraphy when the spine is involved. In some centers, bone scan is still faster and more accessible than MRI. This technique involves a significant amount of radiation exposure44 [Dose range equals to 200–750 chest radiographs; see also Section 2.2 in Supplemental Digital Content, https://links.lww.com/INF/C729 and the American Nuclear Society website (http://www.ans.org/)]. Its specificity may increase with Gallium scan or Indium-labeled leukocytes.50

Finally, when needed, individual cases may be discussed with an experienced radiologist. See Table 7, Supplemental Digital Content, https://links.lww.com/INF/C729 for a summary of imaging studies in BJI in children.

6.4. Differential Diagnosis

Multiple infections and noninfectious diseases may have similar clinical syndromes to BJI and, therefore, should be ruled out, especially when the infection does not progress appropriately and no infectious etiology is isolated. Other types of infection, rheumatologic disease or neoplasias are among the most common or important entities that may mimic BJI. See Table 8, Supplemental Digital Content, https://links.lww.com/INF/C729 for the most common differential diagnosis of BJI.

7. MANAGEMENT

See Table 5 for a summary of recommendations for the management of pediatric BJI.

T5
TABLE 5.:
Principle Scheme for Management of Simple or Uncomplicated and Complex BJI (See Text for Details)

7.1. Introduction

The treatment in most cases of childhood OM, SA and OM-SA can be simplified from the regimen reportedly practiced in many hospitals.29,52,53 Early diagnosis and prompt treatment are needed to avoid complications.5,54 Key factors in the management approach are regional prevalence of CA-MRSA and age of the patient.

  • Initial management includes adequate drainage of pus, collection of specimens for microbiologic studies and prompt initiation of empiric antibiotic therapy.
  • The choice of empiric antimicrobial therapy is based on the most likely causative pathogens according to patient age, immunization status, underlying disease, Gram stain and other clinical and epidemiologic considerations, including prevalence of MRSA.

7.2. Hospitalization

Most children are hospitalized at the start of the infection as IV therapy is generally used. This may be especially important in regions with a high rate of MRSA or PVL-positive S. aureus, worse clinical severity and in high-risk patients such as infants and immunocompromised patients. There is no evidence that BJI can be treated with oral therapy (PO) during the whole course of the disease, although children with milder infections without risk factors for a worse outcome may have a favorable outcome on PO antibiotics. Nevertheless, with the current evidence, we cannot recommend this latter approach.

An alternative approach used by some centers when IV antibiotics are still needed for specific situations is the insertion of a peripheral-inserted central line for once/daily antibiotic treatment at home—outpatient parenteral antimicrobial therapy.55,56 Nevertheless, prolonged IV therapy may be associated with catheter-associated complications and, moreover, oral therapy does not seem to be linked with a higher risk of treatment failure compared with prolonged IV therapy in children with BJI.57,58

7.3. Antibiotic Therapy

7.3.1. Empirical IV Therapy

Any empirical therapy should include coverage of S. aureus. When CA-MRSA prevalence is 10%–15% or higher, this pathogen should be included in the choice of empiric therapy.

Local, up-to-date resistance patterns are required to decide the best initial empirical therapy [Table 14 (Supplemental Digital Content, https://links.lww.com/INF/C729) shows a summary of pathogens with geographical prevalence]. The level of severity may also lower the threshold to initiate anti-MRSA therapy or other adjuvant measures.

See Table 9 in the full, online version (Supplemental Digital Content, https://links.lww.com/INF/C729) for empirical therapy preferences in different European countries.

Other considerations regarding empirical therapy are as follows:

  • Beta-lactams, such as first-generation cephalosporins and cloxacillin or other ASPs, are the drugs of choice for good experience and tolerance.8,23,52,59,60 Clindamycin is a suitable treatment, especially in settings with high rate of CA-MRSA.61
  • Amoxicillin–clavulanate may be an option, although no published data are available and had a higher reported rate of adverse events.59,60
  • Antimicrobials with activity against Kingella should be considered in children <5 years of age, especially in areas with high rates.

Table 6 shows empirical therapy for BJI according to age.

T6
TABLE 6.:
Empirical Therapy by Age

7.3.2. Treatment of MRSA or MSSA PVL-positive S. aureus

Clindamycin can be used if CA-MRSA is a possible cause.61,65–67 Although some authors recommend caution in the case of bacteremic patients,66 others have good experience with clindamycin in this situation.68 Endocarditis and deep venous thrombosis (DVT), as well as inducible macrolide-lincosamide-streptogramin resistance, may be ruled out before treating children with CA-MRSA BJI with clindamycin.65 Some experts may consider treatment of BJI with clindamycin ± rifampin even if MRSA is sensitive to clindamycin. Clindamycin may be combined with a beta-lactam to cover MSSA until bacterial sensitivity is available. It is important to suspect PVL-positive S. aureus (including MRSA) disease if infection fails to respond to empirical treatment, is recurrent, multifocal or associated with a necrotizing process.

In case of severe infection where CA-MRSA or clindamycin-resistance strains are a concern, vancomycin is recommended by the Infectious Disease Society of America (IDSA) Guidelines65 at high dose: 60 mg/kg/d qid—no good data for trough levels in children and, in general, clinical outcome should be followed.69 Nevertheless, evidence of the efficacy of vancomycin in BJI is scarce,70,71 and other antibiotic may be used (daptomycin or linezolid), especially if no initial response or minimum inhibitory concentration to vancomycin ≥2 μg/mL.65,71–73 Rifampin may be added to all 371 but with little evidence. Other options may be quinolones or trimethoprim-sulfamethoxazole (little experience in children)74 ± rifampin. Table 7 shows the empirical therapy according to rate or MRSA.

T7
TABLE 7.:
Initial Empirical Therapy and Rate of MRSA (Beyond 3 Months of Age)

In severe cases or special circumstances, adding a toxin inhibitor antibiotic such as clindamycin, rifampin or linezolid76 may be considered.77 Although data are sparse,71,78 this strategy is considered for adults in IDSA guidelines65 and in children and adults with PVL S. aureus in British guidelines.79 In case of MSSA PVL-positive (PVL+) infections, treatment with first-generation cephalosporins or ASPs “plus” clindamycin might be suitable. Nevertheless, in most situations, the clinicians do not have the PVL results to guide the therapy of BJI.

There are some reports and in vitro studies about the use of intravenous immunoglobulin on severe PVL+ S. aureus BJI infections, but there is not enough evidence to support its general use.80,81

7.3.3. Targeted Therapy

Targeted therapy should be always used once a microorganism has been isolated and its sensitivity determined. Table 8 shows most suitable antibiotic therapy according to specific bacterial isolates.

T8
TABLE 8.:
Pathogens and Antibiotic Treatment (According to Local Resistance Patterns)

7.3.4. Allergy

In case of allergy to beta-lactams, the options are as follows: clindamycin, glycopeptides, quinolones, linezolid and trimethoprim-sulfamethoxazole. The best alternatives to cover the possibility of Kingella infection are trimethoprim-sulfamethoxazole and quinolones (levofloxacin may be superior to ciprofloxacin). Trimethoprim-sulfamethoxazole and quinolones may be suboptimal for Streptococcus pyogenes, although recent studies have indicated a better in vitro susceptibility to the former antibiotic.84

7.3.5. Oral Therapy

Oral therapy following initial IV treatment has been used as equivalent to prolonged IV therapy and may be associated with fewer complications.57,58

Switching to PO Therapy After IV Treatment

Early oral switch has been used8,52,53,68 if the child is showing clinical improvement (although there is limited evidence and variable practice), which may include the following:

  • Afebrile or clear decreased temperature for 24–48 hours
  • Improvement of symptoms, with decreased inflammation and pain
  • Decrease in CRP of about 30%–50% from maximum value
  • No signs of complications, such as metastatic foci (endocarditis, pneumonia, etc.) or DVT
  • Absence of virulent pathogens, such as Salmonella, MRSA or PVL+
  • Negative blood cultures if initially positive
Culture-negative Infections

In culture-negative infections, the recommendation is to continue with an oral antibiotic similar to the class used in IV treatment.

  • In high MRSA regions: clindamycin ± cephalosporin (the latter in younger children)—alternatives for clindamycin may be trimethoprim-sulfamethoxazole, quinolones or linezolid.
  • In low MRSA regions: first/second generation cephalosporin. Clindamycin is a good alternative especially in children >2 years old. Amoxicillin–clavulanate may be an alternative option, but thorough evidence is lacking and the tolerance is worse.
Culture-positive Infections

In culture-positive infections, follow the recommendations listed in Table 8.

According to reviewed sources, there are no good data for how long younger infants and neonates need IV therapy. Most experts would treat newborns, in particular, and young infants, for example, <3 months old, with IV therapy and for a longer total duration (4–6 weeks). Nevertheless, there is some personal experience in switching to PO after a minimum duration of IV therapy (eg, 10–14 days) beyond the neonatal period.

7.3.6. Duration of Therapy

The length of total therapy, IV plus PO, should be on average of 2–3 weeks for SA and 3–4 weeks for OM. Although the evidence is lower for pyomyositis, 2–6 weeks of total therapy (with a few days of IV therapy) may be appropriate for this infection.85

In the following situations, longer therapy may be required (although practice varies, some centers may go up to 4–6 weeks):

  • Resistant or unusual pathogens (eg, MRSA, PVL+ and Salmonella)
  • Newborns and young infants (ie, <3 months)
  • Slow/poor response or complications; complex infections
  • Involvement of pelvis or spinal column86
  • Sepsis or in immunocompromised children

Before stopping treatment, most symptoms should have disappeared and the CRP should be normal (eg, <2 mg/dL). Children with complex disease, underlying problems, ongoing symptoms or immunodeficiency need careful consideration.

7.4. Adjuvant Treatment

One trial has suggested that symptomatic therapy for pain and fever with nonsteroidal anti-inflammatory drugs (NSAID) in large enough doses during the acute phase while signs of inflammation are present is of benefit.29

Although some studies,87 including a randomized, placebo controlled trial,88 appear to have shown a faster recovery in children with SA, widespread adoption of steroids is not recommended until larger prospective studies are performed. Corticosteroids may delay the diagnosis of noninfectious arthritis.

7.5. Surgical Interventions

Surgical Interventions in OM

Studies show that up to 90% of patients with an early OM can be cured with conservative treatment of antibiotics, especially when antibiotics are initiated during the first days of the onset of symptoms.23,29 Surgery is usually not needed (except if aspiration/drainage is required, for instance in the case of abscess) and could in some cases prolong recovery.

Consensus is lacking on the need, extent, timing and procedures for surgical drainage. In the decision process, the following is important:

  • Clinical response to antibiotic therapy30: for example, persistence of fever >72–96 hours or its reappearance
  • Periosteal abscess and persistent fever and CRP elevation
  • Size and position of the abscess, such as in close proximity to a growth plate–although even abscesses >3 mm may have good outcome with only antibiotics4
  • Sequestration or other suspected complications
  • Identification of MRSA or PVL+ S. aureus may increase the need for surgery22,89
  • Chronic OM or presence of prosthetic material

Surgical Interventions in SA4,8,90–96

  • Joint drainage and irrigation is recommended after the diagnosis of SA is suspected. A delay in effective therapy, including drainage, may be associated with worse outcomes. Drainage and antibiotic therapy should be initiated within 5–7 days of the onset of SA to achieve a more favorable prognosis according to some studies.8,93,96 Drainage may be more important in neonates and infants <18 months of age with SA of the hip or shoulder joint.
  • Classically, surgical drainage by arthrotomy has been performed, but arthrocentesis or arthroscopy, depending on the local expertise, may be effective in a number of cases of SA. Both these procedures are minimally invasive compared with arthrotomy. Some orthopedic surgeons prefer arthrotomy because more complete pus removal can be achieved. However, few small studies, 1 prospective and the others retrospective, have shown that arthrocentesis may be an appropriate approach for SA therapy in children, even when shoulder and hip are involved.90–94 In some institutions, many episodes of SA such as those in the knee and ankle, and hip without risk factors,91,94 are managed by arthrocentesis, sometimes with repeated “closed needle aspirations and lavage”—consider surgery if more than 2–3 interventions have to be performed.93,94
  • Arthrotomy may be considered in some SA involving the hip or shoulder in young children (3–6 months),5 longer duration of symptoms at presentation (5–7 days) and with more virulent pathogens (MRSA or PVL+), because the rate of developing complications and sequelae may be higher.11,54,89,97,98 Some studies have found an association between SA of the hip and higher development of sequelae5,99 and, therefore, some authors suggest arthrotomy when this joint is involved.99
  • Arthroscopy has been associated with shorter lengths of hospital stay and may provide improved visualization of the joint space for prognostic purposes.96,100
  • Generally, even after arthrotomy, there is no need for “immobilization” except for pain control or upon risk of fracture, although some orthopedic surgeons recommend this, especially after hip SA to avoid a potential luxation of the joint.
  • There is little evidence to leave a drain in place routinely. If considered due to the extent of infection or difficulty in debridement, drains should be inserted for as short as possible.

7.6. Physical Therapy

Rehabilitation is a very important part in the management of BJI, and especially so in SA and after surgery. Although injury to the area involved should be avoided, prompt mobilization is crucial for the prevention of complications such as rigidity.

  • Depending on the site and severity of the OM, some type of support and/or protection device may help prevent the development of a pathologic fracture.
  • Non-weight bearing is considered essential in the early management for pain control for the short and longer term.
  • Supportive devices (ie, corsets) in case of spondylodiscitis may be recommended.
  • BJI management is often a multidisciplinary approach with orthopedics and adjunctive therapy should be discussed on a case-by-case basis with them.

7.7. Follow-up and Outcome, Complications/Sequelae

Early diagnosis and appropriate treatment are associated with excellent outcome and successful prevention of chronic inflammation and development of sequestra and fistulae.2 Common sequelae are as follows: limping, dismetry, chronic pain, rigidity and chronic inflammation in the absence of an infectious agent (Table 9).

T9
TABLE 9.:
Clinical Outcome BJI: Possible Complications and Sequelae
  • After hospitalization, follow-up by orthopedics and pediatricians with musculoskeletal experience (and especially infants, hips and physis involvement) is recommended at about 2 weeks, 4–6 weeks, 3 months and 12 months after discharge.
  • Consider longer follow-up in children with involvement of the pelvis, the spinal column and hip, or if the physis is affected, especially infants and younger children.
  • Pain-free normal activity is an important end-point before discharge from follow-up.
  • Check-up should include: clinical investigation, CRP, US—radiography only when indicated.
  • Provide NSAID or analgesia as needed.

The identification of Salmonella,82 MRSA or PVL+ bacteria may be related with higher rate of complications and/or sequelae,89,97 although not all studies have shown this.22,67 PVL+ S. aureus (MSSA or MRSA) may also be associated with higher morbidity in pediatric BJI.11,22,67,98 Some authors claim that MRSA virulence may be related to PVL (or other toxin) production, because PVL is more commonly found in MRSA than in MSSA.67,77,98

It is important to look out for DVT in severe S. aureus OM and especially MRSA/PVL+ infection.101 In case of DVT, it is recommended to discuss the best treatment options with a pediatric hematologist.104 Low molecular weight heparin may be started and maintained until the DVT is resolved. For patients with DVT, antibiotics are typically administered for longer periods of time,102 although there is no evidence of which would be the most appropriate length of therapy for this situation.

Please refer to the full, online version (Supplemental Digital Content, https://links.lww.com/INF/C729) of this guideline for the following:

  • Summary of pathogens in BJI with geographical prevalence (Table 14)
  • Summary of antibiotic recommendations in BJI
  • Abbreviations and definitions used in this guideline
  • Review team members’ information and disclosures

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