Bacterial arthritis: Epidemiology, pathogenesis, and microbiology in infants and children

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 epidemiology, pathogenesis, and microbiology of bacterial arthritis in infants and children will be reviewed here. The clinical manifestations, evaluation, diagnosis, treatment, and outcome are discussed separately. (See "Bacterial arthritis: Clinical features and diagnosis in infants and children" and "Bacterial arthritis: Treatment and outcome in infants and children".)

EPIDEMIOLOGY — Bacterial arthritis occurs more commonly in childhood than during other periods of life [2]. The reported incidence of bacterial arthritis in children ranges from 1 to 37 cases per 100,000, depending upon the study population [2-5]. The estimated incidence in the United States is between 3 and 4 per 100,000 children <20 years, based on hospital discharge data [5].

Children younger than five years are affected most frequently [5]. Males are affected more often than females (male-to-female ratio of approximately 1.71) [5]. The hip and knee are the joints most frequently involved.

RISK FACTORS — Risk factors for bacterial arthritis in the neonate (younger than one month) include [3,6-12]:

●Prematurity

●Umbilical vessel catheterization

●Presence of central venous catheters

●Femoral vessel blood sampling

●Osteomyelitis

●Active maternal infection at the time of delivery [13]

Most older infants and children who develop bacterial arthritis are without chronic medical problems [14]. Predisposing factors may include immunodeficiency, joint surgery, hemoglobinopathy, underlying arthritis, and diabetes.

Preexisting joint disease in children with juvenile idiopathic arthritis (JIA, which includes chronic arthritis subtypes formerly called juvenile rheumatoid arthritis) and other arthritis-associated rheumatic diseases (eg, systemic lupus erythematosus, dermatomyositis) may delay the diagnosis of bacterial arthritis [15]. Children and adolescents whose rheumatic disease requires treatment with immunosuppressive therapy may be predisposed to bacterial arthritis with unusual pathogens. (See "Classification of juvenile idiopathic arthritis".)

PATHOGENESIS — Normal joints contain a small amount of synovial fluid, which is highly viscous, clear, and essentially acellular. The synovial membrane is a highly vascular layer of connective tissue that lacks a basement membrane [16].

Microorganisms can enter the joint space by hematogenous spread, direct inoculation, or extension of a contiguous focus of infection (eg, osteomyelitis).

●Hematogenous spread accounts for most cases of bacterial arthritis. The high blood flow and lack of basement membrane in the synovia facilitate entry of bacteria into the joint space during episodes of bacteremia [2]. Bacteremia may occur in association with upper respiratory, skin, or gastrointestinal infection [17-19]. Bacteremia also may occur following joint surgery, joint injection, and instrumentation of the gastrointestinal or genitourinary tracts. During the process of hematogenous spread, bacteria may invade other sites in addition to the joint space (eg, meninges, pericardium, soft tissues), particularly when Haemophilus influenzae type b is involved [20,21].

●Direct inoculation occurs when the joint is invaded by a contaminated object (eg, kneeling or crawling on a sharp object such as a needle) [22] or introduced at the time of joint surgery or injection. Although most cases of bacterial arthritis are caused by a single organism, polymicrobial infections should be considered in patients with direct inoculation [23]. Infection due to direct inoculation may occur after the external wound has healed [24].

●Contiguous extension of infection to the joint space is rare, except in the case of adjacent osteomyelitis. Septic arthritis and osteomyelitis often coexist, particularly with bacterial arthritis of the hip, shoulder, and elbow joints [4,5,25-27]. Most often, this reflects anatomy with the joint capsule extending to, or slightly distal to, the epiphyseal plate, allowing bone infection to invade the joint space.

Differences in the microvascular anatomy of bone have been hypothesized to be an additional cause of concomitant osteomyelitis and septic arthritis in newborns and infants. At birth, nutrient metaphyseal capillaries perforate the epiphyseal growth plate, potentially permitting spread of infection from the metaphysis to the epiphysis and joint surface [28,29]. These vascular channels atrophy postnatally, a process that is usually complete by 18 months [29]. Although metaphyseal capillaries may play a role in contiguous extension in some infants, it is not the sole mechanism since concomitant osteomyelitis and septic arthritis are common in children and adolescents [5,13,25-27,30,31].

Bacteria entering the joint initially deposit in the synovial membrane and produce an acute inflammatory cell response. Because the synovial tissue has no limiting basement plate, bacterial organisms may quickly gain access to the synovial fluid.

Host cells responding to bacterial endotoxin release cytokines, which stimulate the release of proteolytic enzymes and increase leukocyte migration [16]. These products of inflammation destroy the synovium and collagen matrix and inhibit cartilage synthesis. As infection progresses, the joint becomes swollen and red.

The increased joint pressure can interrupt blood flow, leading to avascular necrosis (particularly of the femoral head) [16]. Permanent articular changes may result if prompt surgical drainage is not undertaken [1,16,32]. Distension of the joint capsule may cause laxity, with possible subluxation or dislocation as a sequela [1,33]. (See "Bacterial arthritis: Treatment and outcome in infants and children", section on 'Complications'.)

MICROBIOLOGY — When appropriate cultures are obtained (synovial fluid, blood, and other sites as indicated), the bacterial etiology is confirmed in 50 to 70 percent of cases [14,17,34,35]. The most common causes of bacterial arthritis in children vary depending upon age (table 1).

The most frequently isolated bacteria in children with bacterial arthritis vary depending upon microbiologic techniques, the age and H. influenzae type b (Hib) immunization status of the patients, and the geographic region [36-40]. Associated clinical features or Gram stain may suggest a particular pathogen (table 2).

Gram-positive

Staphylococcus aureus — Staphylococcus aureus is the most common cause of bacterial arthritis detected by culture in all age groups [2,40,41]. Community-associated methicillin-resistant S. aureus (CA-MRSA) bone and joint infections are commonly encountered in the United States, and CA-MRSA osteoarticular infections may be associated with venous thrombosis and pulmonary disease [37,42-44]. (See "Methicillin-resistant Staphylococcus aureus infections in children: Epidemiology and clinical spectrum", section on 'Epidemiology and risk factors'.)

Streptococci — Streptococcal species that cause bacterial arthritis in infants and children include group A beta hemolytic streptococci (GAS, Streptococcus pyogenes), Streptococcus pneumoniae (pneumococcus), and group B streptococci (GBS, Streptococcus agalactiae).

●GAS arthritis occurs primarily in children older than five years [40].

●Pneumococcal arthritis typically occurs in children younger than two years who have no associated extra-articular manifestations (eg, meningitis, pneumonia) [19,45]. In the post-pneumococcal conjugate vaccine era, most cases occur in children without risk factors and are caused by serotypes not included in the 13-valent pneumococcal conjugate vaccine (especially 35B and 33F) [46]. Serotype 33F is included in the 15-valent and 20-valent pneumococcal conjugate vaccines, which were licensed in the United States in 2022 and 2023, respectively (table 3). (See "Pneumococcal vaccination in children", section on 'Conjugate vaccines'.)

●GBS arthritis usually occurs in children younger than three months. (See "Group B streptococcal infection in neonates and young infants", section on 'Other focal infection'.)

Gram-negative — Kingella kingae is increasingly recognized as a cause of gram-negative bacterial arthritis in young children and appears to be the most common cause in parts of Western Europe [4,40,47-49]. Other gram-negative bacteria may cause bacterial arthritis after trauma or in particular hosts (table 2).

Kingella kingae — In many countries, K. kingae is an increasingly recognized cause of bacterial arthritis, particularly in children younger than two to three years of age [13,47,50-53]. It may rarely cause bacterial arthritis in older children and adults [54-57]. Although cases of bacterial arthritis caused by K. kingae were recognized in the 1980s [58-60], the increased recognition of K. kingae as an important pathogen in osteoarticular infections in young children is likely due to improvements in laboratory methods, including polymerase chain reaction detection of bacterial genes and optimization of culture methods [13,47,53,61,62].

Neisseria gonorrhoeae — Neisseria gonorrhoeae is an important cause of bacterial arthritis in newborns and sexually active adolescents [40,63,64]. Gonococcal arthritis in newborns has nonspecific prodromal symptoms: poor feeding, irritability, and fever. The joints below the hip usually are involved (knee, ankles, and metatarsal). (See "Gonococcal infection in the newborn".)

During adolescence, gonococcal arthritis usually occurs as a manifestation of disseminated infection; however, arthritis may be the only sign. Clinical features of disseminated gonococcal infection include fever, rash, and tenosynovitis or small joint arthritis with minimal joint effusion [65-67]. In sexually active females, disseminated gonococcal infection most often occurs in the first week after the onset of menses [68]. (See "Disseminated gonococcal infection".)

Neisseria meningitidis — N. meningitidis usually causes reactive arthritis that is manifested several days into illness. However, N. meningitidis also can cause an infectious arthritis that occurs early in the course of disseminated disease or, occasionally, primary bacterial arthritis without other signs of meningococcal disease [69-71]. N. meningitidis arthritis may be preceded by upper respiratory infection, involve more than one joint, and be associated with a maculopapular rash [67]. (See "Clinical manifestations of meningococcal infection".)

Haemophilus influenzae — Hib may cause osteoarticular infections in young children who did not receive the Hib conjugate vaccine, particularly in areas with low Hib immunization rates [72-76]. Other capsular serotypes of H. influenzae occasionally cause bacterial arthritis [77].

Salmonella — Salmonella species may cause bacterial arthritis in children with sickle cell disease and related hemoglobinopathies [78], children with exposure to reptiles or amphibians, children with gastrointestinal symptoms [79], and children in resource-limited countries. (See "Acute and chronic bone complications of sickle cell disease", section on 'Osteomyelitis and septic arthritis'.)

Others — Other gram-negative organisms occasionally cause bacterial arthritis in particular circumstances.

●Non-Salmonella gram-negative bacilli (eg, Serratia, Aeromonas, Enterobacter, Bacteroides, Campylobacter) may cause arthritis in immunocompromised patients, patients with direct inoculation, and those with a history of recent gastrointestinal or genitourinary instrumentation [23,34,80-84].

●Enterobacter cloacae is a common cause of septic arthritis in children following open or penetrating trauma and is associated with increased risk of complications [23].

●Pseudomonas aeruginosa may cause arthritis in patients with puncture wounds or injection drug use [34,85-87].

●Brucella may cause arthritis in children with foreign travel or other exposure to the organism (usually by consuming unpasteurized dairy products) [88-90].

●Anaerobic arthritis may occur in children with a history of joint surgery, trauma, or oropharyngeal infection [91]. The most common anaerobes causing bacterial arthritis are the anaerobic gram-negative bacilli (Bacteroides fragilis group, Fusobacterium spp, Peptostreptococcus spp, and Cutibacterium acnes). Primary Fusobacterium osteomyelitis with concomitant septic arthritis has also been described [92].

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".)

SUMMARY

●Epidemiology – Bacterial arthritis occurs more commonly in childhood than during other periods of life, particularly in children <5 years. Males are affected more often than females. (See 'Epidemiology' above.)

●Risk factors

•Infants <1 month of age – Risk factors for bacterial arthritis in infants younger than one month include prematurity, umbilical vessel catheterization, central venous catheters, femoral vessel blood sampling, osteomyelitis, and active maternal infection at the time of delivery. (See 'Risk factors' above.)

•Older infants and children – Most older infants and children who develop bacterial arthritis are without chronic medical problems.

●Pathogenesis – The pathogenesis of bacterial arthritis involves entry of bacteria into the joint space (by hematogenous spread, direct inoculation, or extension of a contiguous focus of infection) and the subsequent inflammatory response. Most cases of bacterial arthritis in children result from hematogenous spread or local extension from adjacent osteomyelitis. Septic arthritis and osteomyelitis often coexist, particularly with bacterial arthritis in the hip, shoulder, and elbow joints. (See 'Pathogenesis' above.)

●Microbiology – Staphylococcus aureus is the most common cause of bacterial arthritis in all age groups. Kingella kingae has become a common pathogen in young children and is probably under-recognized. Other bacteria may cause bacterial arthritis in specific clinical settings (table 1 and table 2). (See 'Microbiology' above.)