COMMENTARY

Acute Bacterial Arthritis in Children: New Guidelines

William T. Basco, Jr, MD, MS

DISCLOSURES

Recommendations for Diagnostic Evaluation and Testing

William T. Basco, Jr, MD, MS

A session at the 2024 Pediatric Academic Societies annual meeting reviewed the latest clinical practice guideline for acute bacterial arthritis (ABA) in children, developed by a multidisciplinary panel representing the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America.

These guidelines apply to children aged 1 month to 17 years, and the definition of ABA used throughout the guidelines is bacterial infection of joint fluid along with signs of infection. ABA can be suspected (before diagnostic testing), confirmed (by diagnostic testing), or presumed (diagnostic testing negative but treated owing to clinical suspicion). It's also worth reviewing nomenclature used by the guideline authors when assessing evidence. Where they felt that they had strong evidence, they used the phrase "we recommend." When there was conditional evidence, they used the phrase "we suggest."

Incidence and bacteriology. The incidence of ABA varies between 2 and 10 per 100,000 children. Hips are the most common location, followed by the knees, ankles, elbows, and shoulders. The most common isolates are Staphylococcus aureus, but there is an increasing identification of Kingella species. Overall, there has been a decline in the contributions from Streptococcus pneumoniae and Haemophilus influenzae

Diagnostic testing. The most effective way to diagnose ABA is a combination of clinical history, clinical exam, and laboratory testing. The guideline authors do recommend obtaining a blood culture prior to beginning antimicrobial treatment (a strong recommendation) because pooled evidence suggests a positive blood culture rate of approximately 20%, meaning that in at least 1 in 5 cases, clinicians can appropriately limit the scope of parenteral antibiotics. 

The guidelines also suggest sending blood cultures even if joint fluid is obtained because culture results from these two sources don't always correlate. All cultures should be obtained before antibiotics are begun, if possible. The guidelines conditionally recommend obtaining a C-reactive protein (CRP) level because the combination of CRP values > 20 mg/dL and refusal to bear weight provide a sensitivity > 86% and a specificity of approximately 90% for ABA compared with transient synovitis. If elevated, CRP trends can help assess response to treatment. Clinicians should not obtain a calcitonin level, primarily because it is not more predictive than CRP. 

A CBC should be obtained, not because it is as helpful in ruling out transit synovitis, but because it can be useful in screening for other conditions, including cancer. An erythrocyte sedimentation rate is not recommended because it is nondiscriminatory.

Imaging. Plain radiography of the potentially affected joint and adjacent bones is strongly recommended because it sometimes reveals adjacent osteomyelitis, potentially changing the treatment approach. 

Furthermore, plain films can screen for other etiologies such as fractures, tumors, aseptic necrosis of the femoral head, and other orthopedic problems that can mimic ABA. When the affected joint is the hip or shoulder, ultrasonography is recommended before proceeding to more advanced imaging. High-quality ultrasonography may not be readily available outside of pediatric centers, however. For advanced imaging, the guidelines suggest MRI over other imaging modalities, with a sensitivity of 90%-100% for detecting ABA. MRI is especially helpful in identifying adjacent osteomyelitis.

Invasive sampling. Arthrocentesis to obtainjoint fluid should be performed before the administration of antibiotics, but this is a suggestion, not a recommendation. Obtaining joint fluid by aspiration arthrocentesis may be preferable in sequence even if the plan is to take the patient to the operating room, as it would allow administration of antibiotics in a timely fashion while the patient is waiting for an advanced surgical procedure. A white blood cell count with differential and routine bacterial cultures should be done on the aspirated fluid. Clinicians should collect and test as much fluid as possible to improve culture rates rather than obtaining only a fluid-brushed swab. In fact, placing some of the synovial fluid in a blood culture bottle can help detect more difficult-to-grow bacteria such as Kingella.

Recommendations for Treatment and Follow-up

Timing of antibiotics. On the question of delaying antibiotics to allow invasive joint fluid sampling or to get the patient to the operating room, the guidelines suggest that if the patient is ill-appearing, clinicians should draw blood cultures and begin antibiotics immediately. If the patient does not appear ill, the guidelines suggest delaying antibiotics until joint fluid has been obtained via needle aspiration. That said, the pooled evidence demonstrates a minimal decrease in joint culture yield if antibiotics are given before fluid is obtained for culture. 

Empirical antibiotic choices. Most cases of ABA (42%-70%) are caused by S aureus. Some S aureus joint infections are caused by methicillin-resistant S aureus (MRSA), but the contribution by MRSA has been declining in many communities. While Kingella has been identified more commonly, it is still a relatively low-percentage contributor to ABA. Empirical antibiotic choices should therefore be directed to cover S aureus and also MRSA when the community prevalence is greater than 10%-20% of S aureus isolates locally. 

One other caveat applies to infants aged 6-48 months. In these younger children, the relatively greater contribution of Kingella suggests that clinicians should add ampicillin or a first-generation cephalosporin to empirical coverage. Other bacteria to consider would be group A Streptococcus (GAS), which causes about 10% of ABA across all ages. Fortunately, GAS isolates are very sensitive to the typical antibiotic choices. Neisseria gonorrhoeae causes about 1% of ABA, so suspecting it relies heavily on age of the patient and perhaps sexual activity history. And, of course, Streptococcus pneumoniae will be relatively more common in a nonvaccinated patient. 

No real gold standard exists for treatment of ABA when cultures are negative. The guidelines provide tables with suggested empirical choices and durations of therapy.

MRSA. In the scenario where local MRSA constitutes at least 10%-20% of S aureus isolates, the guidelines recommend clindamycin as the first-line antibiotic. If there are concerns for clindamycin resistance, locally or after initiation of therapy, alternative regimens would include daptomycin, ceftaroline, and linezolid. Ceftaroline has the disadvantage of being available only as an intravenous preparation. If Kingella is strongly suspected, remember that Kingella is commonly resistant to both clindamycin and vancomycin, and many are also beta-lactamase–positive.

Adjunct therapy. If a patient requires an interventional procedure, should they be given intra-articular antibiotics? The guidelines generally recommend against this approach, noting the high cure rate with systemic antibiotics and the theoretical concern for chemical irritation within the joint when antibiotics are directly introduced. Adjunct therapies, such as systemic steroids, are conditionally not recommended. While there is potential benefit, the addition of steroids in the treatment of ABA has not yet demonstrated benefit in high-quality studies. 

Response to therapy. The only recommended laboratory modality to assess treatment response is the CRP level. Physical exam and other measures of clinical improvement are important parameters to follow, but a persistently elevated CRP raises the question of an untreated focus of infection, inadequate antibiotic treatment, or an alternative diagnosis. The guidelines recommend obtaining a CRP level no more often than every 2 or 3 days. Following procalcitonin levels or erythrocyte sedimentation rates is not recommended, nor is the evidence sufficient to recommend following serial CBCs.

Poor responses. Patients are considered to have primary treatment failure if they have not improved clinically within 2-3 days of starting antibiotics. In the case of secondary or delayed failure or relapse, questions such as whether the patient was treated with the right drug, at the right dose, patient adherence to treatment regimen, changes in microbial resistance, or the need for additional drainage all should be considered as potential etiologies of prolonged or recurrent symptoms. The guidelines specifically recommend that clinicians consider all the possible contributing causes before routinely switching antibiotic coverage, because many things may contribute to poor response or delayed recurrence.

Timing of discharge. The guidelines recommend treating until fever has abated, there are no signs of sepsis, and the patient has demonstrated improvement in the physical exam, both in general appearance as well as local symptoms. The guidelines also recommend demonstrating a reduction in the CRP level before discharge. 

Treatment modality at discharge. Data from randomized clinical trials comparing outcomes with IV vs oral antibiotics after discharge are insufficient and primarily observational. However, data suggest that oral treatment is fine for osteomyelitis. Thus, the guidelines recommend transitioning the patient to oral antibiotics at the time of discharge (a strong recommendation). For patients who can't take oral regimens or for whom they are not feasible, the recommendation is to continue IV antibiotics as an outpatient with close monitoring. 

Duration of treatment. Without evidence of osteomyelitis, and with sufficient clinical response as an inpatient, the guidelines recommend 10-14 total days of antibiotic treatment. They recommend against assuming that adjacent osteomyelitis is routinely present. Criteria are lacking for duration of treatment of complicated ABA, so treatment is routinely 21-28 days.

Follow-up imaging. In general, the guidelines recommend against repeat imaging if a patient appears to have recovered sufficiently after appropriate therapy. The guidelines do recommend repeating imaging after 48 hours of initial treatment if the patient has not demonstrated sufficient clinical improvement, but good evidence for this recommendation is lacking. Similarly, there is a general lack of evidence to answer the question of whether a second drainage or washout procedure would be helpful. 

Duration of follow-up. The risk for long-term sequelae of joint infections is < 1%, so patients who respond quickly to treatment with symptom resolution may need only 2-3 weeks of follow-up. For infants, the guidelines suggest 4 months of follow-up. ABA of the hip or shoulder should be followed longer. Patients who experienced a delayed initial diagnosis or treatment may be at higher risk for recurrence. Finally, the presence of resistant organisms should prompt the clinician to consider longer follow-up.

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