Bacterial arthritis in infants and children: Treatment and outcome

INTRODUCTION — 

Infections of the joints (known as septic arthritis, pyogenic arthritis, suppurative arthritis, purulent arthritis, or pyarthrosis) may be caused by bacteria, fungi, mycobacteria, and viruses. The term "septic arthritis" usually refers to bacterial arthritis or fungal arthritis, but bacterial joint infections are most common [1,2].

The treatment and outcome of acute bacterial arthritis in infants and children will be reviewed here. The epidemiology, pathogenesis, microbiology, clinical features, and diagnosis of bacterial arthritis in infants and children; acute hematogenous osteomyelitis in infants and children; and the treatment of arthritis caused by Lyme disease are discussed separately:

●(See "Bacterial arthritis: Epidemiology, pathogenesis, and microbiology in infants and children".)

●(See "Bacterial arthritis: Clinical features and diagnosis in infants and children".)

●(See "Hematogenous osteomyelitis in children: Epidemiology, pathogenesis, and microbiology".)

●(See "Hematogenous osteomyelitis in children: Clinical features and complications".)

●(See "Hematogenous osteomyelitis in children: Evaluation and diagnosis".)

●(See "Hematogenous osteomyelitis in children: Management".)

●(See "Treatment of Lyme disease", section on 'Arthritis'.)

OVERVIEW — 

Bacterial arthritis requires prompt recognition and management. Delays in treatment are associated with long-term damage to bones and joints, particularly when the hip or shoulder joint is involved. (See 'Outcome' below.)

Goals — The goals of treatment include sterilization and decompression of the joint space and removal of inflammatory debris to relieve pain and prevent deformity or functional sequelae [1,3]. Drainage of joint fluid and antimicrobial therapy are the cornerstones of therapy.

Indications for consultation — Children with documented or suspected bacterial arthritis should be managed in conjunction with an orthopedic surgeon who is experienced in treating children. Aspiration of the joint should occur as soon as possible when bacterial arthritis is suspected. Joint aspiration provides synovial fluid for analysis and culture and decompresses the joint. Indications for definitive drainage may include bacterial arthritis of the hip and shoulder, failure to improve after 48 hours of antimicrobial therapy, and persistently positive synovial cultures (if obtained). (See "Bacterial arthritis: Clinical features and diagnosis in infants and children", section on 'Synovial fluid' and 'Drainage' below.)

Given the frequency of contiguous osteomyelitis, antibiotic-resistant pathogens, and culture-negative cases, consultation with an expert in infectious diseases is also recommended, particularly for children with [4]:

●Postoperative infection

●Chronic joint infection

●Penetrating injury (may be associated with unusual pathogens; usually is more complex than hematogenous arthritis)

●Inadequate response to therapy

●Prosthetic joint

●Unusual pathogens (eg, Pasteurella multocida, Cutibacterium acnes [in children with prosthetic joints], fungal pathogens)

●Antimicrobial allergy

●Immunodeficiency or on immunosuppressive treatment

●Sepsis or hemodynamic instability

DRAINAGE — 

Joint drainage is a cornerstone of treatment for bacterial arthritis [5-8]. At the time of presentation, joint infections are essentially closed abscesses. Drainage and lavage are necessary to decompress the joint space and to remove inflammatory debris to preserve synovium and collagen matrix [5,9,10].

Drainage procedures — Drainage can be accomplished by arthrocentesis (needle aspiration), arthroscopy, or arthrotomy [1,11-15].

●Arthrocentesis – Aspiration causes minimal morbidity and, in the older child, may not require general anesthesia [16]. The results of meta-analyses and systematic reviews of the management of children with acute bacterial arthritis indicate a trend toward treating these infections by arthrocentesis alone [17-21]. This may reflect increased experience with the use of ultrasound guidance for these procedures [22]. However, arthrocentesis may provide less satisfactory drainage than arthrotomy or arthroscopy in some cases [22]. For example, in two reviews of the surgical management of bacterial arthritis of the hip and knee in children, additional surgical procedures were more commonly performed when arthrocentesis was the primary drainage procedure [17,19].

In observational studies with adult patients and in a meta-analysis of pediatric studies, the outcome of bacterial arthritis in patients treated with repeated needle aspiration was similar and sometimes better than in those treated with surgical drainage [14,17,23]. Good outcome was defined by restoration of joint function with minimal or no residual pain.

●Arthrotomy – Arthrotomy facilitates thorough debridement of infected tissue, breakdown of loculations, and irrigation of the joint space [9,10,16]. However, arthrotomy requires general anesthesia and is more invasive than arthroscopy or needle aspiration.

●Arthroscopy – Arthroscopy with irrigation and debridement is an alternative to arthrotomy for surgical drainage of bacterial arthritis in uncomplicated cases. Arthroscopy is less invasive than arthrotomy, and good outcomes have been reported in young children [24-27]. However, arthroscopic views may be limited, leading to inadequate irrigation or debridement.

Factors that affect choice of drainage procedure — Decisions regarding the optimal drainage procedure should be individualized according to the site and extent of involvement, duration of symptoms, the suspected organism, and the experience of the surgeon or provider [1,9].

●Hip or shoulder involvement – For children with bacterial arthritis of the hip or shoulder, we continue to prefer open surgical drainage (arthrotomy) to arthroscopy or arthrocentesis.

Delayed or inadequate drainage increases the likelihood of adverse outcomes. Increased intra-articular pressure can compromise the blood supply to the femoral head, resulting in avascular necrosis [28,29]. Given the potential for long-term complications and adjacent osteomyelitis in children with bacterial arthritis of the hip or shoulder [28-30], some surgeons consider open surgical drainage as the optimal approach for thorough debridement, breakdown of loculations, and irrigation of the joint space [31] (See 'Drainage procedures' above.)

The authors of a systematic review of the surgical management of septic arthritis of the hip reported that additional arthroscopy or arthrotomy was required in only 3 percent of cases treated initially with arthrotomy, compared with 15 percent of the hips treated with arthrocentesis and 14 percent of those treated with arthroscopy [18].

Although there are reports of successful treatment of bacterial arthritis of the hip or shoulder with arthroscopic drainage or needle aspiration, these reports generally involved older children, children with methicillin-susceptible Staphylococcus aureus (MSSA), pathogens other than S. aureus, or brief duration of symptoms before presentation [16,27,32-40]. Pending additional high-quality studies, we continue to prefer open surgical drainage in children with bacterial arthritis of the hip or shoulder.

●Other joints – For joints other than the hip and shoulder, arthroscopy and arthrocentesis are reasonable alternatives to arthrotomy [13,18,23,41,42]. If the joint is thoroughly drained during diagnostic aspiration, a single aspiration may suffice [41]. Repeat aspiration may be necessary if fluid reaccumulates. In a retrospective study of 74 children with septic arthritis of the knee in Spain, joint aspiration was successful in all children <12 months of age and in children 12 to 36 months of age who had a C-reactive protein (CRP) <20 mg/L (2 mg/dL) at the time of presentation [43].

●Penetrating trauma – For children with bacterial arthritis and penetrating trauma, arthrotomy permits thorough debridement and removal of any radiolucent foreign bodies, if present [44].

●Concomitant osteomyelitis or large amount of debris or loculations – For children with bacterial arthritis and concomitant osteomyelitis, subperiosteal abscess, or large amount of debris or loculations, arthrotomy is generally preferred because it permits better anatomic evaluation (eg, of the femoral neck in hip joint arthritis) and thorough debridement in a single procedure [44].

●Gonococcal arthritis – Gonococcal arthritis seldom involves hip or shoulder joints and usually resolves without surgical drainage [45].

ANTIBIOTIC THERAPY

Indications — Antibiotic therapy is necessary to sterilize the joint fluid. Empiric antimicrobial therapy should be initiated as soon as possible after blood and synovial fluid cultures have been obtained in infants and children with characteristic clinical and laboratory features of bacterial arthritis [8,11,46].

●Characteristic clinical features include (see "Bacterial arthritis: Clinical features and diagnosis in infants and children", section on 'Clinical features'):

•Newborns and young infants – Clinical manifestations of sepsis (eg, irritability, poor feeding), pseudoparalysis, evidence of discomfort when being handled, or fever without a focus

•Older infants and children – Fever and monoarticular pain, swelling, and limited range of motion

●Characteristic laboratory features include (see "Bacterial arthritis: Clinical features and diagnosis in infants and children", section on 'Laboratory evaluation'):

•Elevated peripheral white blood cell (WBC) count and C-reactive protein (CRP); neither of these parameters have sufficient specificity to confirm a diagnosis of septic arthritis, but CRP is useful for monitoring treatment responses

•Elevated synovial fluid WBC count (>20,000 cells/microL) with a predominance of neutrophils

•Organism identified on Gram stain of synovial fluid

The differential diagnosis also must be carefully considered to identify disorders with clinical features similar to bacterial arthritis that do not require joint drainage or prolonged antibiotic therapy (eg, transient synovitis, Lyme arthritis, juvenile idiopathic arthritis). (See "Bacterial arthritis: Clinical features and diagnosis in infants and children", section on 'Differential diagnosis'.)

Empiric parenteral therapy

Factors in choice of regimen — Empiric therapy for children of all ages must provide coverage for S. aureus (the most common cause of bacterial arthritis in the United States and a globally important pathogen) [8,15]. Kingella kingae is a common pathogen in septic arthritis occurring in preschool-aged children [15,47,48]. Approximately 95 percent of these cases occur between the ages of 6 and 36 months, but cases of septic arthritis caused by Kingella are occasionally identified in older children [49,50]. The current Infectious Diseases Society of America (IDSA)/Pediatric Infectious Diseases Society (PIDS) treatment guidelines endorse using an upper age limit of 48 months for including K. kingae in the selection of antimicrobial therapy [15]. Coverage for additional pathogens may be necessary based on the child's age (table 1), history and physical examination findings (table 2), and Gram stain results (table 3) [1,3,44,51].

An overall assessment of the patient's clinical stability is also important because bacterial arthritis may be associated with sepsis in a small fraction of cases. Empiric therapy can be altered when the susceptibility pattern of the causative bacterium is known.

Few randomized controlled studies have evaluated antibiotic regimens for bacterial arthritis. All antibiotics that have been studied readily enter the joint fluid after systemic administration; intra-articular injection of antibiotics is unnecessary, potentially painful, and not recommended [1,15]. The joint fluid concentration for most penicillins and cephalosporins averages 30 percent of the serum concentration at the time of peak serum concentration, and, because of slow efflux from the joint fluid, may exceed serum concentration immediately before the next dose [52-56].

Children younger than three months of age — Empiric therapy for bacterial arthritis in infants <3 months of age should be directed against S. aureus, group B Streptococcus (GBS), and gram-negative bacilli (table 1). (See "Bacterial arthritis: Epidemiology, pathogenesis, and microbiology in infants and children", section on 'Microbiology'.)

For empiric parenteral therapy in children younger than three months with suspected bacterial arthritis, we generally provide combination therapy with an antistaphylococcal agent and either a third-generation cephalosporin or cefepime (table 4 and table 5). Appropriate regimens vary with the clinical presentation and risk factors for methicillin-resistant S. aureus (MRSA) or coagulase-negative staphylococci (algorithm 1).

For infants with allergy or intolerance to cephalosporins (very uncommon in this age group), we suggest consultation with an expert in pediatric infectious diseases.

●Signs of sepsis – For infants <3 months of age with signs of sepsis (eg, tachycardia, poor perfusion, hypotension), some contributors to this topic provide empiric therapy with (algorithm 1):

•Vancomycin plus one of the following:

-Cefotaxime (preferred if available)

-Ceftazidime

-Ceftriaxone (for infants who are not hyperbilirubinemic or receiving intravenous [IV] calcium-containing solutions [57])

-Cefepime

Other contributors add nafcillin or oxacillin to the above regimen.

●No signs of sepsis but with risk factors for MRSA or coagulase-negative staphylococci – Risk factors for MRSA include care in the intensive care unit for >1 week; birthing parent with (or suspected to have) infection or colonization with community-acquired S. aureus; and increased prevalence of MRSA at the admitting institution (eg, ≥10 percent of S. aureus isolates are methicillin resistant). Prematurity and prolonged or recurrent bacteremia with coagulase-negative staphylococci despite antibiotic therapy are the primary risk factors identified for bacterial arthritis with these organisms in neonates [58-60].

For infants without signs of sepsis but with risk factors for MRSA or coagulase-negative staphylococci, we provide empiric therapy with (algorithm 1):

•Vancomycin plus one of the following:

-Cefotaxime (preferred if available)

-Ceftazidime

-Ceftriaxone (for infants who are not hyperbilirubinemic or receiving IV calcium-containing solutions [57])

-Cefepime

At some institutions, clindamycin is used as an alternative to vancomycin if <10 percent of S. aureus isolates are clindamycin resistant and the infant has localized infection with no signs of sepsis. Other experts may use a different threshold for clindamycin resistance.

●No signs of sepsis and no risk factors for MRSA or coagulase-negative staphylococci – For infants without signs of sepsis and without risk factors for MRSA or coagulase-negative staphylococci, appropriate regimens include either:

•Combination therapy with (algorithm 1)

-One of the following antistaphylococcal agents: vancomycin, nafcillin, or oxacillin; plus

-One of the following gram-negative agents: cefotaxime (preferred if available), ceftazidime, or ceftriaxone (for infants who are not hyperbilirubinemic or receiving IV calcium-containing solutions [57])

Cefazolin is an alternative antistaphylococcal agent for infants age one to three months in whom central nervous system infection has been excluded.

•Monotherapy with cefepime (a fourth-generation cephalosporin)

Children three months of age and older — Empiric therapy for bacterial arthritis in children ≥3 months of age should be directed toward S. aureus and, for those between 6 and 36 months of age, K. kingae (table 1).K. kingae appears to be more common than S. aureus in young children in several Western European countries and is increasingly recognized as a cause of septic arthritis in the United States. The rising incidence of K. kingae is likely due to improved culture and deoxyribonucleic acid (DNA) detection methods [49,61].

Coverage for Haemophilus influenzae, Neisseria gonorrhoeae, Salmonella spp may be necessary in select populations (table 2).

Hemodynamically unstable children — For severely ill children (eg, those with hemodynamic instability) who are ≥3 months of age, we suggest empiric combination therapy with either of the following combinations (table 3):

●Vancomycin plus ceftriaxone plus one of the following: nafcillin, oxacillin, or cefazolin

●Vancomycin plus cefepime

This combination therapy broadly covers the most likely pathogens to cause septic arthritis complicated by septic shock (MRSA, methicillin-susceptible S. aureus [MSSA], and Neisseria meningitidis). Nafcillin, oxacillin, or cefazolin are superior to vancomycin for treatment of serious MSSA infections. Ceftriaxone or cefepime provide activity against N. meningitidis.

We provide empiric antimicrobial therapy for other pathogens as indicated. For children with septic arthritis and hemodynamic instability who are unable to tolerate penicillin and cephalosporin antibiotics, we use vancomycin in combination with a carbapenem or fluoroquinolone until gram-negative bacteremia is excluded. (See 'Additional coverage for other pathogens' below.)

Hemodynamically stable children — Agents that provide coverage for S. aureus and other gram-positive pathogens in children who are hemodynamically stable include cefazolin, clindamycin, nafcillin/oxacillin, and vancomycin. The agent of choice depends on the severity of illness, local prevalence of community-associated MRSA (CA-MRSA), the susceptibility of CA-MRSA isolates to clindamycin, and suspicion for other pathogens (table 3) [2,8,62,63].

K. kingae is usually susceptible to cephalosporins (eg, cefazolin, cefotaxime, ceftriaxone), but it is consistently resistant to vancomycin and often resistant to clindamycin and antistaphylococcal penicillins (eg, oxacillin, nafcillin) [64,65]. If a child between 6 and 48 months of age is being treated with an antistaphylococcal agent to which Kingella is resistant (eg, vancomycin), a cephalosporin should be added.

Initial antimicrobial therapy for bacterial arthritis is usually administered parenterally. Drug doses are provided in the table (table 4).

●Communities where <10 percent of S. aureus isolates are methicillin-resistant – For children in these communities, we suggest cefazolin, nafcillin, or oxacillin. Cefazolin also provides coverage for K. kingae.

For children in these communities who are unable to tolerate penicillin and cephalosporin antibiotics, we suggest clindamycin if <10 percent of S. aureus isolates are clindamycin resistant. Other experts may use different thresholds for methicillin or clindamycin resistance.

●Communities where ≥10 percent of S. aureus isolates are methicillin-resistant – For children in these communities, we suggest either clindamycin or vancomycin [2,8,62]. Other experts may use a different threshold for methicillin-resistance.

•We suggest vancomycin for children who have underlying frequent contact with the health care system or who were hospitalized in the past six months because these children may have an increased risk of clindamycin resistance.

•We suggest vancomycin when ≥10 percent of S. aureus isolates in the community have either constitutive or inducible resistance to clindamycin. Other experts may use a different threshold for clindamycin resistance. Vancomycin also provides coverage for penicillin-nonsusceptible Streptococcus pneumoniae.

•We suggest clindamycin when <10 percent of S. aureus isolates in the community are resistant to clindamycin. Clindamycin also covers many penicillin-resistant S. pneumoniae (although a large proportion of serotype 19A isolates are resistant to multiple drugs, including clindamycin).

Alternatives to vancomycin or clindamycin when MRSA is a concern include linezolid or daptomycin (if the child is ≥1 year of age and has no concomitant pulmonary involvement) [8,62,66]. Ceftaroline is active against many pathogens that cause septic arthritis in children (including K. kingae) [67] and is under investigation for use in septic arthritis and osteomyelitis in children, but data are limited [15,68,69].

In one study comparing antimicrobial agents for osteoarticular infections, outcomes were similar among 169 Finnish children with culture-proven acute osteoarticular infections who were treated with clindamycin versus first-generation cephalosporins [70]. In this study, nearly all cases were caused by infection with MSSA (84 percent), Streptococcus pyogenes (9 percent), or S. pneumoniae (5 percent); no cases of Kingella infection were identified.

Additional coverage for other pathogens

●Other Gram-negative organisms on Gram stain – A third-generation cephalosporin should be added to empiric antistaphylococcal therapy if gram-negative organisms are identified on Gram stain. This will provide coverage for K. kingae and the other most common gram-negative organisms (including N. meningitidis) that cause septic arthritis in children. Empiric antistaphylococcal therapy should be continued because Gram stain results are subject to observer misinterpretation.

●Penetrating trauma or history of penetrating trauma – Penetrating trauma may cause polymicrobial infection. Empiric therapy should include coverage for Pseudomonas aeruginosa as well as S. aureus. Options for empiric therapy include cefepime alone (for coverage against P. aeruginosa and MSSA) or combination therapy with cefepime or ceftazidime plus an agent with activity against MRSA (eg, clindamycin, vancomycin). Pathogen-directed therapy should include agents directed against all organisms recovered.

●Incomplete H. influenzae type B (Hib) immunization – Coverage for Hib (eg, cefotaxime, ceftriaxone) should be added to the empiric regimen for children <2 years of age who are incompletely immunized against Hib (table 6) in areas where Hib immunization rates are low but is not necessary for those in areas with high Hib immunization rates. In the United States, local immunization coverage rates may be available from the Centers for Disease Control and Prevention or the American Academy of Pediatrics.

●Children at risk for penicillin-nonsusceptible pneumococcal arthritis – Empiric coverage for penicillin-nonsusceptible S. pneumoniae (eg, cefotaxime, ceftriaxone) may be warranted in children [71]:

•Younger than five years with incomplete pneumococcal immunization (table 6)

•Age two years or older with medical conditions that increase the risk of invasive pneumococcal disease (table 7)

•Who received antibiotics within four weeks of diagnosis of bacterial arthritis

In the era of routine pneumococcal vaccination, most cases of pneumococcal arthritis occur in children without risk factors and are caused by serotypes not included in the pneumococcal conjugate vaccine (especially 35B and 33F, which were not included in the 10-valent or 13-valent vaccine) (table 8) [72]. In the United States, the 15-valent and 20-valent pneumococcal conjugate vaccines, which contain serotype 33F, were licensed for use in children in 2022 and 2024, respectively. (See "Pneumococcal vaccination in children", section on 'Conjugate vaccines'.)

●Sickle cell disease – Coverage for Salmonella (eg, cefotaxime, ceftriaxone) should be routinely added to the empiric regimen for children with sickle cell disease or related hemoglobinopathies. (See "Evaluation and management of fever in children and adults with sickle cell disease", section on 'Empiric antibiotic therapy'.)

●Recent gastrointestinal surgery or complex urinary tract anatomy – Patients with recent gastrointestinal surgery or complex urinary tract anatomy are at risk for infection with enteric gram-negative organisms or Enterococcus. Addition of ampicillin and either 1) a third- or fourth-generation cephalosporin (eg, cefotaxime, ceftriaxone, cefepime) or 2) an aminoglycoside (eg, gentamicin) to the initial empiric regimen may be warranted.

●Sexually active adolescents – Coverage for N. gonorrhoeae (eg, ceftriaxone) should be added to antistaphylococcal coverage in sexually active adolescents [73]. (See "Disseminated gonococcal infection", section on 'Initial antimicrobial therapy'.)

Presumptive treatment for chlamydia should also be given unless it has been excluded microbiologically.

●Injection drug users – Organisms that cause infection among injecting drug users (IDU) vary markedly between different communities. P. aeruginosa has been frequently reported among IDUs with bacterial arthritis. If P. aeruginosa arthritis is a consideration, our initial empiric regime includes ceftazidime as well as antistaphylococcal coverage with nafcillin/oxacillin or vancomycin. (See "Pseudomonas aeruginosa skin and soft tissue infections" and "Principles of antimicrobial therapy of Pseudomonas aeruginosa infections".)

Pathogen-directed therapy — Pathogen-directed therapy is based upon culture and susceptibility results (table 9). Consultation with an expert in infectious diseases is suggested for children with an inadequate response to therapy, unusual organisms (eg, P. multocida, C. acnes, fungal pathogens), immunocompromised individuals [74], and/or drug allergies. (See 'Indications for consultation' above.)

Negative cultures — Historically, no organisms were identified in 30 to 50 percent of children with clinical bacterial arthritis [54,75-77].

●Improvement with empiric therapy – In patients who demonstrate clinical and laboratory improvement with empiric therapy, the initial empiric therapy is continued. Patients who are immunocompetent and fully immunized against Hib and S. pneumoniae (table 6) may be switched to oral therapy if the oral regimen provides the same spectrum of coverage as the initial parenteral empiric regimen. (See 'Oral therapy' below.)

●No improvement with empiric therapy – In patients who do not demonstrate clinical and laboratory improvement with empiric therapy, additional infectious agents and diagnoses other than bacterial arthritis must be considered. (See 'Treatment failure' below.)

Oral therapy — In infants and children ≥1 month, parenteral therapy is continued at least until clinical and laboratory improvement have been demonstrated, after which the balance of antibiotic therapy can be administered orally [15,78]. As long as the patient has demonstrated improvement, successful treatment does not require a minimum duration of parenteral therapy. In randomized and observational studies, treatment of bacterial arthritis in children with IV antibiotics for short periods (approximately seven days) followed by oral therapy was as successful as longer courses of parenteral therapy [79-81]. (See 'Response to therapy' below.)

Prerequisites — Our prerequisites for switching from parenteral to oral therapy include [4,80-85]:

●The child is ≥1 month of age (for infants younger than one month of age, we provide the entire course of antimicrobial therapy parenterally); the gastrointestinal absorption of oral antibiotics in neonates is unpredictable [86,87].

●The child has improved as expected with parenteral therapy (eg, decreased swelling, tenderness, and erythema; improved joint mobility; decreased or absent fever; decreased CRP). (See 'Response to therapy' below.)

●The child is immunocompetent and fully immunized against Hib and S. pneumoniae for their age (table 6).

●The child has demonstrated the ability to swallow and retain an appropriate oral medication; the initial doses of oral therapy should be administered while the child is in the hospital to ensure that the drug is tolerated.

●The patient and caregiver(s) have received appropriate education, are committed to the follow-up schedule, and are expected to adhere to the antimicrobial regimen. (See 'Outpatient follow-up' below.)

●The pathogen has been identified and an oral agent with appropriate coverage is available, or, if cultures are negative, the child has responded as expected to empiric parenteral therapy and an oral regimen with a spectrum similar to the parenteral regimen is available. (See 'Response to therapy' below.)

●The clinical course has been uncomplicated.

Choice of oral regimen

●Agent(s) – The choice of agent(s) for oral therapy depends upon whether an organism was isolated from or detected in the synovial fluid, blood, or other culture. Additional considerations include the bioavailability and palatability of the oral medication. Consultation with an expert in infectious diseases may be helpful in choosing the optimal oral agent, particularly if the child has an unusual pathogen (eg, P. multocida, C. acnes, fungal organisms) or allergy to antibiotics. (See 'Indications for consultation' above.)

•Organism isolated – When an organism is isolated, the susceptibility pattern is used to determine an appropriate drug. If K. kingae is detected by polymerase chain reaction (PCR) only, an antibiotic that K. kingae is typically susceptible to (table 9) is chosen.

•Organism not isolated – When an organism is not isolated, oral therapy is directed toward the most likely pathogen(s) given the child's age (table 1) and clinical presentation (table 2). The chosen regimen should have a spectrum similar to that provided by the parenteral therapy that was associated with improvement. As examples, a child who improved on cefazolin may be switched to cephalexin; a child who improved on parenteral clindamycin could be switched to oral clindamycin.

●Dose – Given the possibility of concomitant osteomyelitis and the relatively low penetration of penicillins and certain cephalosporins into bone, antibiotics administered orally for bacterial arthritis are generally given in higher doses than those used for treatment of other infections and recommended in package inserts (table 10) [88-91]. Doses of penicillins, cephalexin, and cefadroxil can be increased to 100 to 150 mg/kg per day without serious adverse side effects [70,88]. Monitoring drug levels may be helpful in exceptional cases if there is a concern about adequate absorption or adherence to the treatment regimen. Nonetheless, it is not generally necessary; clinical examination and laboratory monitoring for markers of inflammation provide sufficient evidence of the efficacy of treatment. (See 'Drug monitoring' below.)

●Administration of first dose – We advise that the initial dose of oral therapy be administered while the child is in the hospital to ensure that the drug is tolerated. The child may be discharged home when they are able to tolerate the oral antibiotic and it is clear that the caregiver can administer oral therapy as prescribed. (See 'Outpatient follow-up' below.)

Drug monitoring

●Adequacy of therapy – We do not usually monitor drug levels for adequacy of therapy in children with bacterial arthritis. The use of oral antimicrobial agents to complete treatment for septic arthritis has been commonplace for decades and is nearly always associated with success [36]. Measurement of antibiotic levels may be helpful in rare patients if there is a concern regarding adequate absorption or adherence to the treatment regimen.

●Adverse effects – Potential adverse effects of prolonged high-dose antibiotic therapy include pancytopenia, leukopenia, hepatitis [85,92], hypersensitivity reactions, hepatotoxicity, kidney dysfunction, and antibiotic-associated diarrhea [86,87,93-96]. The likelihood of these events varies by the agents used; for example, neutropenia is most commonly encountered with beta-lactam antimicrobial agents and inhibitors of folate metabolism (estimated at approximately 10 occurrences per 1000 patient-weeks) [87].

The author of this topic obtains a weekly complete blood count (CBC) with differential and serum aminotransferases while the patient is receiving beta-lactam antibiotics (eg, penicillins, cephalosporins). Other contributors only obtain serum aminotransferases in children with underlying liver disease. Patients receiving linezolid for more than two weeks should have weekly CBC monitoring. (See 'Outpatient follow-up' below.)

We acknowledge that the likelihood of adverse drug events is low during the 10 days to three weeks of therapy required for most cases of acute bacterial arthritis in children. Additional studies are needed to evaluate the costs, consequences, and value of this monitoring. (See 'Total duration' below.)

Outpatient parenteral therapy — Outpatient parenteral antimicrobial therapy (OPAT) may be warranted for children ≥1 month of age who have improved as expected with parenteral therapy but do not meet the prerequisites for oral therapy. (See 'Prerequisites' above.)

Insertion of a percutaneously inserted central catheter facilitates prolonged administration of parenteral antibiotics and can be used for OPAT [4]. However, catheter-related complications (eg, malfunction, displacement, bloodstream infection) occur in 30 to 40 percent of children with osteoarticular infections who are treated with OPAT [97,98].

Total duration — The total duration of antimicrobial therapy for bacterial arthritis depends upon the pathogen and response to therapy.

We provide the following general guidelines:

●S. aureus – Minimum of two to three weeks

●S. pneumoniae, GBS, group A Streptococcus – Ten days to two weeks

●K. kingae, N. meningitidis, H. influenzae – Two to three weeks

●Other gram-negative pathogens (eg, Salmonella) – Three weeks, particularly in the setting of penetrating trauma or gastrointestinal surgery

●Culture-negative arthritis – Two weeks

Antimicrobial therapy may be discontinued if the CRP has returned to normal by the conclusion of the antibiotic course, magnetic resonance imaging (MRI) was performed at presentation and did not show evidence of osteomyelitis, and the patient has steadily improved [15]. The same approach is used for culture-negative septic arthritis.

We advise the inclusion of a plain radiograph before discontinuing antibiotics if the pathogen is MRSA, the patient fails to improve markedly within two weeks of initiating antibiotics, or when the septic joint is the shoulder or hip. These patients are at greater risk for concomitant osteomyelitis, which occurs in as many as 64 percent of bacterial arthritis cases [63,70,82,99-102] and is associated with a worse prognosis than bacterial arthritis alone [103]. (See 'Prognostic factors' below.)

Radiographic findings suggestive of osteomyelitis include lytic lesions (image 1) and periosteal elevation (image 2), thickening, or new bone formation [104]. Osteomyelitis may require surgical intervention or prolongation of antibiotic therapy. (See "Hematogenous osteomyelitis in children: Evaluation and diagnosis", section on 'Advanced imaging' and "Hematogenous osteomyelitis in children: Management".)

We suggest consultation with an infectious diseases specialist to determine whether a longer antibiotic course is necessary for patients with bacterial arthritis of the hip [41] and for arthritis caused by Enterobacteriaceae or other unusual organisms [8,82,105]. (See 'Indications for consultation' above.)

The suggested treatment durations are based on studies performed in the 1970s. A multicenter randomized open-label trial performed in Finland between 1983 and 2005 suggested that 10 days of antimicrobial therapy may be adequate for patients with culture-positive bacterial arthritis without adjacent osteomyelitis who demonstrate clinical improvement and either CRP <2 mg/dL (20 mg/L) or two normal CRP levels [41]. However, no cases of MRSA infections were encountered in this series, and 15 percent of children with hip involvement required extension of therapy beyond the planned duration [106]. Given these limitations and the paucity of data from infants (in whom septic arthritis of the hip is frequently associated with sequelae), we continue to treat bacterial arthritis for two to three weeks for most pathogens, and three weeks as a minimum for S. aureus.

ADJUNCTIVE THERAPIES

Analgesia — Pain management is an important aspect of therapy for bacterial arthritis. Opioid therapy may be necessary during initial hospitalization; consultation with the pain management service may be helpful. After discharge, acetaminophen or ibuprofen may be used for pain control [4].

Physical therapy — Attention must be paid to joint position and rapid mobilization to prevent contractures and promote optimal nutrition to the articular cartilage. Physical therapy may be helpful in children who are reluctant to use the joint.

Once discharged home, the child initially may require a wheelchair or walker and continued physical therapy.

Anti-inflammatory agents — The inflammatory response is an important component of the pathogenesis of bacterial arthritis and accounts for at least a portion of the long-term morbidity. Some experts recommend routine nonsteroidal anti-inflammatory drugs (NSAIDs), but there are no data to demonstrate that NSAIDS improve recovery or alter outcomes. The author of this topic recommends nonselective NSAIDs if necessary for pain management.

We do not routinely suggest adjunctive glucocorticoid therapy for children with septic arthritis. Although randomized trials and observational studies comparing dexamethasone with placebo in children with septic arthritis have suggested potential benefits, long-term outcomes were inconsistent [107-110]. A meta-analysis that included two randomized trials (a total of 149 patients) found both trials to be at high risk of attrition bias and selective outcome reporting [110]. Additional limitations include the absence of cases of methicillin-resistant S. aureus and the relatively prolonged duration of parenteral antibiotics in some patients. Moreover, the effects of dexamethasone were not compared with those of nonsteroidal anti-inflammatory agents, which are recommended as adjunctive therapy by some experts.

The 2023 clinical practice guideline from the Pediatric Infectious Diseases Society (PIDS) and Infectious Diseases Society of America (IDSA) also recommends against the use of adjuvant corticosteroids to treat children with acute bacterial arthritis based on data showing the potential for minimal beneficial effects and risk of serious harm [15].

RESPONSE TO THERAPY

Monitoring response — The response to therapy is assessed with serial clinical and laboratory evaluations. During hospitalization, we monitor clinical status (eg, fever; joint pain, swelling, erythema, and mobility) at least daily. We monitor peripheral white blood cell (WBC) count and/or C-reactive protein (CRP) every two to three days and/or if clinical status worsens. We monitor synovial fluid WBC count and culture (if repeated aspirations are necessary).

Monitoring during outpatient oral or parenteral therapy is discussed below. (See 'Outpatient follow-up' below.)

Expected response — Clinical and laboratory improvement is indicated by:

●Resolution of fever – Fever usually resolves within three to five days of initiation of treatment [4,79].

●Improved joint symptoms – Improvement in joint symptoms (pain, swelling, erythema, mobility) usually occurs within two days of initiation of treatment. The time required for resolution of symptoms and sterilization of the joint fluid is proportional to the duration of symptoms before initiation of appropriate therapy and the synovial fluid WBC count at the time of diagnosis [111-113].

●Normalization of the peripheral WBC count and decreased erythrocyte sedimentation rate (ESR) and/or CRP – CRP is more useful than ESR for monitoring acute response to treatment. WBC counts, if initially abnormal, normalize within one week of initiation of treatment [114]. Even with appropriate treatment, the ESR may continue to rise for three to five days, whereas CRP peaks within 36 to 50 hours of onset of infection and quickly falls to normal with appropriate therapy [9,114].

●Decrease in synovial fluid WBC count and sterilization of synovial fluid – In joints that initially were drained with needle aspiration, synovial fluid may reaccumulate, requiring repeated drainage. Infected knees, in particular, may continue to accumulate fluid for 7 to 10 days. When available (from repeat aspiration or a surgical drain), serial synovial fluid analyses should demonstrate sterilization and a decreasing WBC count within one to two days.

Treatment failure — Treatment failure may be indicated by:

●Lack of clinical improvement

●CRP that continues to rise three to five days after initiation of therapy

●Persistently elevated CRP, peripheral WBC count, or synovial fluid WBC count

●Failure to sterilize the synovial fluid in the expected period of one to two days (if repeat cultures are obtained)

Patients who do not respond to empiric or pathogen-directed therapy as expected should be reevaluated. They may require arthrotomy and/or adjustment of antimicrobial therapy.

Reevaluation should generally include magnetic resonance imaging for evidence of osteomyelitis with abscess; review of the history for exposure to unusual organisms (eg, P. multocida, C. acnes) or penetrating trauma; and reconsideration of other conditions in the differential diagnosis. (See "Bacterial arthritis: Epidemiology, pathogenesis, and microbiology in infants and children", section on 'Microbiology' and "Bacterial arthritis: Clinical features and diagnosis in infants and children", section on 'Differential diagnosis'.)

For patients who do not improve after 48 hours of antibiotic therapy or have persistent positive cultures despite appropriate antimicrobial therapy and multiple needle aspirations, arthrotomy may be necessary to ensure thorough debridement of infected tissue, breakdown of loculations, and irrigation of the joint space.

For patients with failure to improve despite appropriate pathogen-directed therapy, it may be helpful to monitor drug levels to ensure adequate serum levels. (See 'Drug monitoring' above.)

For patients with negative cultures, more aggressive attempts to isolate or identify unusual pathogens and fastidious organisms (eg, K. kingae) may be warranted, if not already done (table 2). This may include:

●Aspiration of any involved soft tissue or bone biopsy for histopathologic staining and bacterial culture.

●Molecular testing is especially helpful for identifying K. kingae in synovial fluid that is culture negative. (See "Bacterial arthritis: Clinical features and diagnosis in infants and children", section on 'Synovial fluid'.)

●Appropriate serologic testing for children with potential exposure to Coccidioides or Brucella. (See "Coccidioidomycosis: Laboratory diagnosis and screening" and "Manifestations and treatment of nonmeningeal extrathoracic coccidioidomycosis" and "Brucellosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

●Tuberculosis testing if Mycobacterium tuberculosis is suspected. (See "Tuberculosis disease in children: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis'.)

If the additional evaluation does not identify an organism, changing or broadening the empiric therapy to include organisms not covered by the initial regimen may be indicated. For example, in patients initially treated with vancomycin, clindamycin, nafcillin, or oxacillin, changing the antibiotic to cefazolin will address the possibility that K. kingae is the causal organism.

OUTPATIENT FOLLOW-UP — 

We see children who are being treated for bacterial arthritis as outpatients approximately one week after discharge from the hospital and at one- to two-week intervals thereafter.

We monitor them for continued clinical improvement (including the need to initiate or continue physical therapy) and the author of the topic monitors for complications related to high-dose antibiotic therapy, such as cytopenias, hepatitis [92], impaired liver or kidney function, antibiotic-associated diarrhea, and pseudomembranous colitis.

The author of the topic obtains a complete blood count (CBC) with differential and C-reactive protein (CRP) at each visit. It is also reasonable to obtain a biochemical profile, including serum aminotransferases, weekly while the patient is receiving beta-lactam antibiotics, although some experts only obtain serum aminotransferases in children with underlying liver disease. If patients are not improving as expected after being transitioned to oral therapy, it may be advisable to revert to intravenous (IV) therapy. (See 'Treatment failure' above.)

After treatment is discontinued, children generally should be monitored for long-term complications at routine well-child care visits. Those who are at high risk of damage to cartilage (eg, delayed recognition of septic arthritis of the hip for three or more days) should be monitored by an orthopedic surgeon with experience in pediatrics. (See 'Complications' below.)

OUTCOME

Complications

●Short-term complications – Short-term complications of bacterial osteoarticular infections include sepsis, septic shock, deep vein thrombosis, and septic pulmonary emboli [115,116].

●Long-term complications – Potential long-term complications of bacterial arthritis include [1,28,30,104,117-120]:

•Avascular necrosis

•Joint laxity, subluxation, deformation, dislocation, or destruction

•Limited range of motion of the joint

•Limb-length discrepancy or angular deformities (if the growth plate is involved)

•Enlargement of the femoral head (coxa magna) in bacterial arthritis of the hip

•Pathologic fractures

•Premature osteoarthritis

The estimated rate of complications ranges from 10 to 29 percent, depending upon the patient population, the involved joint, and the duration of follow-up (prolonged follow-up may be necessary to detect some complications) [1,16,39,76,102,104,121-123]. Studies published after 2015 have reported lower rates of complication (4 to 5 percent), possibly reflecting more awareness and/or improved management strategies [39,102].

Even with appropriate management, up to 40 percent of patients with hip involvement and 10 percent of patients with knee involvement develop significant complications [12,124-126].

Prognostic factors — In observational studies, the following factors were associated with long-term complications [75,76,105,123,126-132]:

●Duration of symptoms before treatment, particularly if >4 to 7 days (ie, a delay in diagnosis)

●Involvement of the hip

●Involvement of the hip or shoulder with concomitant osteomyelitis

●Age less than one year, particularly less than one month

●Isolation of S. aureus or Enterobacteriaceae compared with other pathogens

Factors that do not appear to be related to outcome include:

●The mode of drainage, provided that adequate drainage is achieved

●The choice of antibiotic, provided that it is effective against the infecting organism

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Septic arthritis and osteomyelitis in children".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

●Basics topic (see "Patient education: Septic arthritis (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Overview – Bacterial arthritis requires prompt recognition and management. Drainage of joint fluid and antimicrobial therapy are the cornerstones of therapy. (See 'Overview' above.)

●Drainage – Decisions regarding the optimal drainage procedure should be individualized. We prefer arthrotomy for children with bacterial arthritis of the hip or shoulder, penetrating trauma, concomitant osteomyelitis, and/or large amount of debris or loculations. For other joints, arthroscopy and needle aspiration are reasonable alternatives. (See 'Drainage' above.)

●Antibiotic therapy – Antibiotic therapy is necessary to sterilize the joint fluid. Antibiotics should be administered as soon as possible after blood and synovial fluid cultures have been obtained. (See 'Antibiotic therapy' above.)

•Empiric parenteral therapy – We include coverage for Staphylococcus aureus in the empiric regimen for children of all ages (algorithm 1 and table 3). We add coverage for Kingella kingae for children from 6 months to 48 months. Coverage for additional pathogens may be necessary based on the child's age (table 1), history and physical examination findings (table 2), and Gram stain results (table 3). Initial antimicrobial therapy for bacterial arthritis is usually administered parenterally (table 4). (See 'Empiric parenteral therapy' above.)

•Pathogen-directed therapy – The antimicrobial regimen can be tailored to a specific pathogen when culture and susceptibility results are available (table 9). Children whose cultures remain negative and improve with empiric therapy usually are continued on the empiric parenteral regimen. (See 'Pathogen-directed therapy' above.)

•Route and total duration of therapy – In infants <1 month of age, we provide the entire course of antimicrobial therapy parenterally. Infants who are age one month or older and children may be switched to oral therapy (table 10) if they have demonstrated clinical and laboratory improvement and meet prerequisites for oral therapy. (See 'Oral therapy' above and 'Outpatient parenteral therapy' above and 'Total duration' above.)

S. aureus arthritis is usually treated for two to three weeks; other causes of bacterial arthritis and culture-negative arthritis are usually treated for ten days to three weeks. Antimicrobial therapy may be discontinued if the C-reactive protein (CRP) has returned to normal by the conclusion of the antibiotic course, an MRI was performed at presentation and did not show evidence of osteomyelitis, and the patient has steadily improved. (See 'Total duration' above.)

We advise the inclusion of a plain radiograph before discontinuing antibiotics if the pathogen is methicillin-resistant S. aureus (MRSA), the patient fails to improve markedly within two weeks of initiating antibiotics, or when the septic joint is the shoulder or hip.

●Response to therapy – Children receiving appropriate antimicrobial therapy generally demonstrate clinical improvement within three to five days. Clinical improvement is demonstrated by decreased fever; improved joint pain, swelling, erythema, and range of motion; and decreased peripheral white blood cell (WBC) count, CRP, and synovial fluid WBC count and culture (if follow-up synovial fluid is obtained). (See 'Response to therapy' above.)

Patients who do not respond to treatment as expected should be reevaluated. They may require additional diagnostic approaches, arthrotomy, and/or adjustment of antimicrobial therapy. (See 'Treatment failure' above.)

●Outpatient follow-up – We see children who are being treated for bacterial arthritis as outpatients approximately one week after discharge from the hospital and at one- to two-week intervals thereafter. We monitor them for clinical improvement and possible complications of high-dose antibiotic therapy. We obtain a complete blood count with differential and CRP at each visit. It is also reasonable to obtain a biochemical profile, including serum aminotransferases, weekly while the patient is receiving beta-lactam antibiotics, although some experts only obtain serum aminotransferases in children with underlying liver disease. (See 'Outpatient follow-up' above.)

●Outcome – Residual joint dysfunction is a major morbidity for children with septic arthritis. Factors related to poor outcome include duration of symptoms before treatment, involvement of the hip, involvement of the hip or shoulder with concomitant osteomyelitis, and age younger than one year. (See 'Outcome' above.)