By Kenna Riley PharmD Candidate,
Bacterial arthritis (e.g., septic arthritis) is caused by bacteria entering the joint from the bloodstream, causing infection and inflammation of the joint and synovial fluid.1 It requires prompt antibiotic treatment to prevent severe outcomes, such as irreversible joint damage. In 2023, the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA) published a guideline to provide recommendations on diagnosis and treatment strategies to improve patient outcomes.1 The purpose of this writing is to summarize the key points in that guideline and summarize any emerging data.
Antimicrobial Recommendations
Bacterial arthritis generally affects a single joint (e.g., knee) and presents with sudden onset fever, joint pain, swelling, and immobility.1 Those who are most at risk include children under 3 years, males, those with recent trauma, and individuals with a weakened immune system (e.g., prematurity, sickle cell disease, or HIV).1To improve the likelihood of identifying a pathogen, it is recommended, when clinically reasonable, to obtain a full work up (e.g., blood culture, synovial fluid culture/analysis, C-reactive protein, imaging) prior to the initiation of empiric antibiotics.1
Staphylococcus aureus is the most common cause of bacterial arthritis in children.1 Kingella kingae is another causative pathogen, that has up until recently been unable to be identified, but with recent technology with improved diagnostics this is now feasible.2 K. kingae is most commonly seen in children 6 months to 5 years old.1,2 These two pathogens luckily is often present a bit differently. When bacterial arthritis is caused by S. aureus it typically has a rapid and aggressive onset, with joint pain that quickly worsens over 24 to 48 hours.1,2 Whereas K. kingae infections have a more gradual onset with symptoms at presentation often being less severe.2
Treatment of Bacterial Arthritis
PIDS/IDSA guidelines recommend empiric therapy to cover S. aureus.1 It is important to consider pediatric methicillin-resistant S. aureus (MRSA) rates, especially community-associated MRSA as these vary by region. In areas with low MRSA prevalence (e.g., <10-15% of community-acquired S. aureus infections), guidelines recommend empiric treatment with either a first-generation cephalosporin (e.g., cefazolin) or an anti-staphylococcal penicillin (e.g., nafcillin, oxacillin).1 In contrast, in regions with high MRSA prevalence, it’s essential to empirically include an agent with strong MRSA activity, such as clindamycin (if high rates of susceptibility) or vancomycin. In those who are 6 months to less than 4 years old, it is suggested to ensure coverage also includes K. kingae (which is already covered if cefazolin is chosen) by adding an agent such as ampicillin to either clindamycin or vancomycin therapies.1
When choosing an antibiotic, it’s important to understand each antibiotic’s risks vs benefits. Starting with the antibiotics used in areas with lower MRSA rates. Penicillins and cephalosporins are time-dependent killing drugs and efficacy is best predicted by the amount of time the antibiotic’s concentration remains above the minimum inhibitory concentration (T>MIC). The anti-staphylococcal penicillins require frequent administration every 4 to 6 hours and are associated with adverse effects such as phlebitis, interstitial nephritis, as well as hematologic suppression (e.g., anemia, neutropenia) when used for longer periods (e.g., > 14 days). In contrast, cefazolin offers a more convenient dosing schedule, administered every 8 hours, while still maintaining a strong safety profile and efficacy against MSSA and K. kingae.
Another key antibiotic often used in treatment, particularly for suspected methicillin-resistant S. aureus (MRSA) infections, is vancomycin. This is a good first choice when highly reliable MRSA coverage is needed. Vancomycin is the preferred antimicrobial agent for clindamycin-resistant CA-MRSA infections when initial parenteral therapy is required.1 It requires therapeutic drug monitoring due to its narrow therapeutic index and nephrotoxicity risk. On the other hand, clindamycin is a great alternative with excellent oral bioavailability, making it optimal when susceptible, especially for outpatient management. However, clindamycin resistance may be a concern, depending on the local resistance rates and must be weighed into decision making. Ultimately, the choice between these two agents is determined by the severity of the infection, local susceptibility rates, and the need to balance their risks and benefits.
It is also important to note that the guidelines do not recommend the use of adjunctive corticosteroids. There is insufficient evidence to support their benefit, and they may suppress the immune system, hindering the body’s ability to clear the infection.
In addition to what therapies to use and avoid, therapy duration is another important consideration. The guidelines state that the total duration of therapy is variable and depends on a patient’s clinical and laboratory response to treatment, as well as the specific pathogen. For patients who show rapid clinical improvement and a trending decrease in C-reactive protein (CRP) by the end of the first treatment week, a shorter course of 10 to 14 days is often sufficient.1 However, if a patient has a slower clinical response, has inadequate source control, or has persistently elevated CRP levels, a longer course of 21 to 28 days may be preferred to ensure the infection is completely cleared.1 This approach allows for adjustments in therapy duration as the patient’s condition evolves, ensuring both efficacy and patient safety.
Areas of Uncertainty & Emerging Evidence
While the new guideline provides a strong framework, it also highlights areas of clinical uncertainty. Future research is needed to improve the diagnostic accuracy of laboratory tests, better define the role of advanced molecular pathogen identification, and establish an optimal duration for antibiotic therapy. These gaps underscore that while guidelines are a vital resource, they also serve as a road map for future research to refine and improve the care of children with septic arthritis.
The 2023 PIDS/IDSA guidelines for pediatric acute bacterial arthritis are recently published and there has been limited new evidence that would significantly result in many changes. A notable study was published in 2024 that supports initial oral therapy. A nationwide, randomized controlled trial from September 2020 to June 2023 in Denmark evaluated non-severe uncomplicated bone and joint infections (~40% were joint infections) comparing initial therapy of intravenous ceftriaxone 100 mg/kg/day once daily or oral therapy with amoxicillin/clavulanate 100/12.5 mg/kg/day in three daily doses in children 3 months to 5 years or dicloxacillin 200 mg/kg/day in four daily doses in children 5 to 17 years. Patients in both groups were changed to standard dose oral therapy after at least 3 days of therapy and demonstration of clinical and laboratory improvement. Approximately 40% of the patients had joint infections with 25% identifying a specific pathogen (S. aureus 14-16% – only 1 of which had MRSA and K. kingae 5-9%). Total duration of antibiotics for joint infections were 12.6 (10.3 – 19.4) high dose oral therapy and 10.6 (9.8-14.2) days initial intravenous therapy. No patients met the study designed criteria of sequelae after 6 months demonstrating non-inferiority of the high-dose oral therapy. With regards to adverse effects nausea was statistically higher in those in the high dose oral therapy group (11.2% vs 2.5%). No serious complications were noted.3 This study provides some additional prospective evidence that intravenous therapy may not always be necessary for treatment of MSSA and K. kingae bone and joint infections in children.
About the author: Kenna Riley is a Doctor of Pharmacy candidate at the University of Connecticut. This post was written as part of her Advanced Pharmacy Practice Experience under the guidance of her professor, Jennifer Girotto PharmD, BCPPS, BCIDP, who also reviewed and edited the piece.
References
1. Woods CR, Bradley JS, Chatterjee A, et al. Clinical practice guideline by the pediatric infectious diseases society (PIDS) and the infectious diseases society of america (IDSA): 2023 guideline on diagnosis and management of acute bacterial arthritis in pediatrics. J Pediatric Infect Dis Soc. 2024;13(1):1–59. doi: 10.1093/jpids/piad089.
3. Gouveia C, Duarte M, Norte S, et al. Kingella kingae displaced S. aureus as the most common cause of acute septic arthritis in children of all ages. Pediatr Infect Dis J. 2021;40(7):623–627. doi: 10.1097/INF.0000000000003105.
4. Nielsen AB, Holm M, Lindhard MS, et al. Oral versus intravenous empirical antibiotics in children and adolescents with uncomplicated bone and joint infections: A nationwide, randomised, controlled, non-inferiority trial in denmark. Lancet Child Adolesc Health. 2024;8(9):625–635. doi: 10.1016/S2352-4642(24)00133-0.