Septic Bacterial Arthritis Essentials of Diagnosis The classic presentation is acute onset of painful, warm, and swollen joint, usually monarticular and affecting large weight-bearing joints. Synovial fluid white blood cell counts usually >50,000 cells/mm 3 with over 80% neutrophils. Positive synovial fluid culture. Staphylococcus aureus is the most common cause of septic arthritis in native joints. General Considerations The reported incidence of septic arthritis varies from 2–10 per 100,000 per year in the general population, with substantially higher rates in patients with rheumatoid arthritis (RA) or joint prostheses (both 30–70 cases per 100,000 per year). The incidence of bacterial arthritis is significantly higher among children than adults. Septic (bacterial) arthritis is a medical emergency, and delay in diagnosis and treatment can lead to irreversible joint destruction and an increase in mortality. Even with the advent of better antimicrobial agents and techniques of joint incision and drainage, the rate of permanent joint damage from septic arthritis is 25–50%. The case fatality rate for bacterial arthritis also remains high at 5–15%, with increased mortality rates seen in the setting of polyarticular septic arthritis, underlying RA, and in immunocompromised states. Risk factors for the development of bacterial arthritis include chronic arthritic syndromes, prosthetic joints, parenteral drug use, extremes of age, diabetes mellitus, and immunocompromised conditions (Table 47–1). Table 47–1. Risk Factors and Mechanisms of Infection in Bacterial Arthritis Risk Factor Mechanism of Infection Comments
Transcript
Septic Bacterial Arthritis
Essentials of Diagnosis
The classic presentation is acute onset of painful, warm, and swollen joint, usually monarticular and affecting large weight-bearing joints.
Synovial fluid white blood cell counts usually >50,000 cells/mm3 with over 80% neutrophils.
Positive synovial fluid culture. Staphylococcus aureus is the most common cause of septic arthritis in native joints.
General Considerations
The reported incidence of septic arthritis varies from 2–10 per 100,000 per year in the general population, with substantially higher rates in patients with rheumatoid arthritis (RA) or joint
prostheses (both 30–70 cases per 100,000 per year). The incidence of bacterial arthritis is significantly higher among children than adults.
Septic (bacterial) arthritis is a medical emergency, and delay in diagnosis and treatment can lead to irreversible joint destruction and an increase in mortality. Even with the advent of better antimicrobial agents and techniques of joint incision and drainage, the rate of permanent joint damage from septic arthritis is 25–50%. The case fatality rate for bacterial arthritis also remains high at 5–15%, with increased mortality rates seen in the setting of polyarticular septic arthritis, underlying RA, and in immunocompromised states. Risk factors for the development of bacterial arthritis include chronic arthritic syndromes, prosthetic joints, parenteral drug use, extremes of age, diabetes mellitus, and immunocompromised conditions (Table 47–1).
Table 47–1. Risk Factors and Mechanisms of Infection in Bacterial Arthritis
Risk Factor Mechanism of Infection Comments
Rheumatoid arthritis (RA)
Local and systemic factors play a role
Damaged joint serves as nidus for infection
Immunosuppressive medications predispose to infection, especially previous use of oral or intra-articular steroids
RA is complicated by septic arthritis in 0.3–3% of patients
Polyarticular septic arthritis in RA has >50% mortality rate
Staphylococcus aureus most likely organism
Prosthetic joint Foreign body serves as nidus for infection, especially for pathogens that lay down biofilms or glycocalyx layer (eg,
Rates of infection have decreased over the past 30 years
Higher incidence in revision arthroplasty
Staphylococcus epidermidis)
No microvasculature in artificial joint
(see text for details)
Injection drug use; indwelling lines; chronic skin infections
Recurrent bacteremia with subsequent hematogenous seeding of joints
Patients on chronic hemodialysis, with chronic indwelling lines, with repeated skin injections (eg, insulin), or with chronic skin infections are susceptible
The knee is the most commonly infected joint in injection drug users, but also see axial joint infections, including sternoclavicular and sacroiliac joint involvement
S. aureus (often methicillin-resistant) most common cause in injection drug users
Pseudomonas aeruginosa seen in
10% of cases
Crystal-induced arthritis (gout, pseudogout)
Local factors Joint damage from crystals Synovial fluid acidosis in
Crystal-induced arthritis can cause high synovial WBC counts without infection
Presence of crystals does not rule out infection
Infection-mediated destruction of articular cartilage can rarely elicit crystals in synovial space
Severe osteoarthritis, Charcot joint, hemarthroses
Joint disorganization, chronic synovitis, and blood within synovial space can provide a nidus for infection
Always send a bloody synovial effusion for culture to exclude infection
Chronic, systemic disease (eg, lupus, cancer, diabetes mellitus, other immunosuppressive
Impaired host defenses from chronic illness, including phagocytic deficiencies
S aureus and gram-negative bacilli most common organisms
In lupus, functional hyposplenism may
conditions, including extremes of age [children <5 or adults >65])
Medications for chronic illnesses (eg, glucocorticoids in lupus) predispose to infection
occur, leading to susceptibility to encapsulated organisms (eg, Neisseria gonorrhoeae, Salmonella, Proteus)
Intra-articular injection (or arthrocentesis)
Direct inoculation of the offending organism
Most common agents are skin flora, including S epidermidis and S aureus
HIV infection Immunosuppression and an increased tendency to develop bacteremia with localized infections
Even in asymptomatic HIV infection, underlying risk factors for acquiring HIV, such as injection drug use or hemophilia, can predispose
Sexual activity Predisposes to localized gonococcal infection, which may disseminate to cause joint and skin disease
DGI 2–3 times more common in women than men, especially after menses or in postpartum period
Terminal complement deficiencies also predispose to DGI.
DGI, disseminated gonococcal infection; WBC, white blood cell.
Pathogenesis
Bacterial pathogens reach the joint spaces by hematogenous spread (>50% of cases), by direct inoculation, or by spread from adjacent bony or soft-tissue infections. Although skin infections are the most common predisposing infections to joint infections, transient bacteremia from respiratory, gastrointestinal, or genitourinary infections can also lead to septic arthritis. Bacteria enter the closed joint space, and within hours the synovium becomes infected, leading to synovial membrane proliferation and infiltration by polymorphonuclear and other inflammatory cells. This inflammatory response in turn leads to enzymatic and cytokine-mediated degradation of the articular cartilage, neovascularization, and the eventual development of granulation tissue. Without appropriate treatment, irreversible subchondral bone loss and cartilage destruction occur within a few days of the initial infection.
Clinical Findings
Symptoms and Signs
The classic presentation of bacterial arthritis is the abrupt onset of a painful, warm, and swollen joint. More indolent presentations are seen in patients with preexisting rheumatic illnesses or immunocompromised states. An obvious joint effusion, moderate to severe joint tenderness to palpation, and marked restriction of both passive and active motion are common signs of septic arthritis.
A patient with an acute monarticular arthritis should be considered to have septic arthritis until proven otherwise. Nongonococcal bacterial arthritis is monarticular in 80–90% of cases, with polyarticular involvement (10–20%) carrying a poorer chance of survival. Polyarticular septic arthritis is more likely to occur in patients with RA or other systemic connective tissue diseases or in the syndrome of overwhelming sepsis. Infectious monarthritis typically involves the knee (40–50%), hip (13–20%), shoulder (10–15%), wrist (5–8%), ankle (6–8%), elbow (3–7%), and the small joints of the hand or foot (5%). Bursitis, especially olecranon and prepatellar, may be the first manifestation of septic arthritis in patients with RA.
Septic arthritis manifests with fever in 60–80% of cases, although the temperature elevation is not usually pronounced. Twenty percent of patients with fever have shaking chills that usually correspond to waves of bacteremia. Cough, gastrointestinal symptoms, or dysuria may represent symptoms of the antecedent infection. Indeed, a preceding source of infection, such as pneumonia, otitis, bronchitis, pharyngitis, or cutaneous, gastrointestinal, or genitourinary infection, can be identified in up to 50% of septic arthritis cases.
Physical Examination
The initial physical examination for septic arthritis should determine whether the source of inflammation and pain is articular or periarticular (specifically, localized to skin, bursae, or tendons). Septic arthritis produces warmth, swelling, and tenderness of the involved joint, and attempts at passive and active motion of the joint usually produce considerable discomfort. Similar findings occur in noninfectious forms of severe inflammatory arthritis, such as acute gout. In contrast, cellulitis and inflammation of bursae and tendons do not cause joint effusions, and passive motion of the adjacent joint usually does not elicit severe pain unless there is stretching of an inflamed tendon. Because septic arthritis can involve more than one joint, all joints should be examined for warmth, swelling, deformity, range of motion, pain on motion, and tenderness.
Septic arthritis of the sacroiliac (SI) joint is often difficult to distinguish from infection in the hip because both present with fever and pain upon ambulation and because examination of the SI joints is difficult (see Chapter 1). Moreover, findings of SI septic arthritis can be subtle and can be mistaken for the syndrome of a protruded disk or a paraspinous muscular strain. Similarly, infection of the shoulder joint is often difficult to identify given the usual lack of a visible effusion. Adults with shoulder infections tend to be elderly, with multiple risk factors for the development of septic arthritis. Infections of the sternoclavicular joint most often occur in injecting drug users; an abscess of the chest wall or in the intrathoracic extrapleural space will develop in 20% of patients with septic arthritis of the sternoclavicular joint. Septic olecranon bursitis is distinguished from infection of the elbow joint by the presence of swelling and erythema overlying the olecranon process and the absence of joint pain with passive extension of the elbow. Infection of the olecranon bursa often follows minor trauma
to the region, which leads to inoculation of organisms (usually S aureus) into the bursal space.
Laboratory Findings
Peripheral Counts and Cultures
Peripheral white blood cell (WBC) counts are elevated in bacterial arthritis approximately two-thirds of the time. The erythrocyte sedimentation rate and C-reactive protein are usually elevated and may be useful to monitor during treatment, especially in children with septic hip infections. Approximately 40–50% of patients with septic arthritis have associated bacteremia, so blood cultures should be obtained prior to the administration of antibiotics. Targeted cultures from extra-articular sites, such as respiratory, cutaneous, gastrointestinal, or genitourinary sites, should also be collected after a careful history and physical examination.
Synovial Fluid Analysis
Synovial fluid analysis is critical for the definitive diagnosis of septic arthritis. Synovial fluid is usually obtained by emergent arthrocentesis, with fluoroscopic or computed tomographic (CT) guidance if necessary (see Chapter 2). An open surgical procedure may be required to obtain synovial fluid and biopsies for the diagnosis of bacterial arthritis, especially in suspected sternoclavicular, hip, or shoulder infections or in the presence of prosthetic joints. Of note, arthrocentesis is contraindicated if the needle must pass through an area of cellulitis, heavily colonized skin lesions (eg, psoriatic plaques), or infection of any kind because of the risk of introducing bacteria into the joint space. Bacteremia is also a relative contraindication for the performance of arthrocentesis.
Once synovial fluid has been collected, the following analyses should be performed (see Chapter 2):
Appearance: Look for color and clarity of the fluid, since purulence or turbidity or both suggest a septic process.
Cell count and differential: The joint fluid in nongonococcal septic arthritis has more than 50,000 WBC/mm3 in 50–70% of cases. Low synovial fluid cell counts may be seen early in the process of infectious arthritis, in the setting of partially treated infections, or in immunosuppressed patients. The majority of WBCs in infected synovial fluid are neutrophils (usually >80% polymorphonuclear cells).
Gram stain for organisms: A positive Gram stain is diagnostic for septic arthritis (highly specific), but a Gram stain that is negative for bacteria does not rule out an infected joint. The Gram stain is positive 50–75% of the time in nongonococcal bacterial arthritis, with gram-positive bacterial arthritis more likely to stain positive than gram-negative bacterial arthritis. The Gram stain should be used to guide presumptive therapy.
Culture: Bacterial culture of the synovial fluid is positive in 70–90% of cases of nongonococcal arthritis, depending on the organism. Inoculating synovial fluid into blood culture bottles rather than solid media increases the yield of culture growth and decreases the contamination rate.
Microbiology: Table 47–2 shows the typical pathogens of nongonococcal bacterial arthritis and risk factors for their acquisition. Staphylococcus aureus is the most common cause of septic monarthritis in native joints (60–70%) (Figure 47–1). The
remaining causes of septic arthritis include streptococcal species, gram-negative rods, and anaerobes in relatively constant proportions. Hematogenous infection can result from transient bacteremia secondary to a remote infection or a surgical procedure, including dental work or respiratory, gastrointestinal, or genitourinary manipulations. Group A streptococci are often isolated from the infected joint after procedures in the oral cavity, whereas gastrointestinal procedures can lead to bacteremia with non–group A streptococcal species, gram-negative bacilli, or anaerobes.
Table 47–2. Major Bacterial Organisms Implicated in Nongonococcal Septic Arthritis and the Percentage of Adult Infections Attributable to Each Pathogen
Organism % of Adult Infections
Comments
Staphylococcus aureus
60–70% Most common pathogen in native joints and late prosthetic joint infections
Rates of methicillin-resistant S aureus are increasing in injection drug users and in the community
Streptococcal species
15–20% Group A streptococci most common streptococcal species implicated in septic arthritis
Usually preceded by primary skin or soft-tissue infection
Incidence is increasing of non–group A -hemolytic streptococci (eg, groups B, C, and G streptococci), especially in immunocompromised hosts or following gastrointestinal or genitourinary infections
S pneumoniae infectious arthritis is still quite rare
Gram-negative bacilli
5–25% Most common in neonates, infants younger than 2 months, the elderly, injection drug users, and the chronically ill (diabetes mellitus, cancer, sickle cell anemia, connective tissue disorders, and renal transplant recipients and other immunosuppressed conditions)
Begin as urinary tract or skin infections, with subsequent hematogenous spread to a single joint
Haemophilus influenzae arthritis has decreased markedly since routine H influenzae type b childhood vaccination
Anaerobes 1–5% Common species include Bacteroides, Propionibacterium acnes (skin flora), and various anaerobic gram-positive cocci
50% of anaerobic arthritis is polymicrobial
Predisposing factors: diabetes mellitus, immunocompromise, or postoperative wound infections, especially following total joint replacement or joint arthroplasty
Suspect if synovial fluid is foul smelling or air is present in the joint space radiologically
Collect cultures under anaerobic conditions and incubate for at least 2 weeks
Staphylococcus epidermidis
Rare in native joints
Most common agent in early postoperative prosthetic joint infections
Forms glycocalyx layer over foreign surface Organism often difficult to eradicate without joint
removal
Brucella species Rare B melitensis most common Brucella species implicated
Uncommon in the United States, but more prevalent worldwide
Risk factors: ingestion of unpasteurized milk or cheese or occupational exposures (eg, farmers and meat packers)
Causes monarthritis or an asymmetric peripheral oligoarthritis
Sacroiliitis and spondylitis also common Diagnose with scintigraphy, computed tomography
scan, polymerase chain reaction, and/or positive blood or joint cultures
Treatment courses lengthy and involve antimicrobial combinations
Mycoplasma Rare More common in children than adults Seen in the immunocompromised, particularly
agammaglobulinemia
Figure 47–1.
Gram stain of an inflammatory exudate showing the clustered gram-positive cocci of Staphylococcus aureus.
(Image contributed by Dr. Thomas F. Sellers and is in the public domain; from the Centers for Disease Control Public Health Image Library [http://phil.cdc.gov].)
Imaging Studies
Plain Radiographs
Plain radiographs are of little diagnostic usefulness in acute septic arthritis but are often obtained as a baseline and to exclude contiguous osteomyelitis. Radiographs will usually reveal only soft-tissue swelling; in cases of infection with Escherichia coli or anaerobic organisms, however, radiographs may demonstrate gas formation within an untapped joint. In late septic arthritis (at least 8–10 days after infection), films may show subchondral bone destruction, periosteal new bone formation, joint space narrowing, or osteoporosis.
Computed Tomography
Because the hip, shoulder, sternoclavicular, and SI joints are difficult to palpate and to aspirate, evaluation of these joints usually requires CT or magnetic resonance imaging (MRI). CT is preferred for the sternoclavicular joint. CT scans may demonstrate early bone erosions, reveal soft-tissue extension and detect effusions, and facilitate arthrocentesis of the hip, shoulder, sternoclavicular, and SI joints.
Magnetic Resonance Imaging
MRI scans demonstrate adjacent soft-tissue edema or abscesses and may be especially helpful in detecting septic sacroiliitis. MRI can also detect the early bone erosions of incipient contiguous osteomyelitis.
Scintigraphy
Scintigraphy makes use of various agents, such as labeled WBCs, technetium colloid, or immunoglobulin, to highlight areas of infection. The drawback of this imaging technique in the diagnosis of septic arthritis is the rate of false-positives with contiguous soft-tissue infections; scintigraphy cannot reliably differentiate septic from aseptic joint inflammation. False-positive scans can also result from underlying fracture or a recent operation. Given this low specificity, scintigraphy is rarely used as the imaging study of choice for the diagnosis of septic arthritis.
Gallium Scan
Gallium accumulates where there is a extravasation of serum proteins and leukocytes and is better than scintigraphy in distinguishing infection from mechanical damage. Gallium scans have shown increasing utility in the diagnosis of septic arthritis and the identification of concurrent osteomyelitis.
Differential Diagnosis
Septic arthritis usually presents as acute monarthritis, and occasionally as an acute oligoarthritis or a polyarthritis. The differential diagnoses of these syndromes are reviewed in Chapter 4, but several points warrant emphasis here. The diagnosis of acute monarthritis is infection unless proved otherwise. Differentiating infection from crystal-induced arthritis can be particularly difficult, since acute flares of pseudogout or gout can also cause fever, peripheral leukocytosis, and markedly elevated synovial cell counts. Bacterial superinfection can complicate crystal-induced arthritis, although this is rare. A history of recurrent monarthritis, typical podagra, or radiologic evidence of chondrocalcinosis are all suggestive
of crystal-induced arthritis. However, only arthrocentesis with culture of the synovial fluid and analysis for crystals can definitively distinguish septic arthritis from crystal-induced arthritis.
Treatment
Early diagnosis is the key to successful treatment of septic arthritis; delay in instituting appropriate antibiotic therapy and débridement measures almost invariably leads to poor outcomes. The two mainstays of treatment are drainage and intravenous antibiotic therapy. Progressive joint mobilization will also help prevent some of the long-term complications of septic arthritis.
Drainage
The management of septic nongonococcal arthritis requires hospitalization for drainage of the infected joint. The joint must be thoroughly drained to decrease the number of inflammatory cells, which produce cytokines and proteolytic enzymes that cause permanent joint damage. Early arthroscopic lavage, débridement, and drain insertion have largely replaced the standard procedure of performing daily aspirations of the joint. Response to therapy can be gauged by following the synovial fluid cell counts and culture results over the subsequent days of hospitalization.
Open surgical drainage and débridement (arthrotomy) may be required for the following indications:
Failure to respond to more conservative therapy in 5–7 days. Coexistent osteomyelitis that needs surgical intervention. Involvement of joints that are difficult to drain using more conservative approaches,
such as hips, shoulders, or SI joints. Involvement of a prosthetic joint (see section on prosthetic joint infections, below) Difficulty in performing adequate drainage of the joint with needle aspiration or
arthroscopic manipulations. Refusal of the patient to accept repeated needle aspirations or catheter drainage (eg,
young children). Open drainage is the initial procedure of choice in children with septic arthritis of the
hip.
Antibiotics
After the initial diagnostic joint aspiration, intravenous antibiotics should be immediately administered. Empiric antibiotic therapy is based on either the initial Gram stain results or the clinical situation (Table 47–3) in suspected bacterial arthritis. Antibiotics are usually administered for a total of 6 weeks for a native joint infection. Intra-articular antibiotic instillation has not been shown to be beneficial and may lead to a chemical synovitis.
Table 47–3. Initial Antibiotic Therapy for Septic Arthritis Based on Synovial Gram Stain or Clinical Situation
Synovial Fluid Gram Stain or Clinical
Situation
Antibiotic Therapy
Gram-positive cocci Use IV vancomycin initially due to increasing rates of methicillin-resistant S aureus (MRSA) in the community (dosing: 10–15 mg/kg per dose administered q12h or q8h; typical regimen is 1 g IV q12h initially with doses subsequently adjusted to keep serum vancomycin troughs
in the 15–20 g/mL range) Switch to high-dose third-generation cephalosporin (eg,
ceftriaxone 2 g IV q24h; ceftizoxime 1 g IV q8h) or appropriate penicillin class if methicillin-sensitive S aureus (MSSA) or streptococcal growth; if MSSA, can use nafcillin 2 g IV q4h; if penicillin-sensitive streptococcal species, can use penicillin 24 million units qd or 4 million units IV q4h
Oral options: ciprofloxacin (750 mg PO bid) plus rifampin (450 mg PO bid); give bactericidal intra-articular concentrations in combination, but these should be used only for prosthetic joint infections; increasing data are available on linezolid (600 mg PO bid) in MRSA joint infections
Gram-negative bacilli Use IV therapy with an aminoglycoside (eg, gentamicin 1 mg/kg IV q8h or tobramycin 1.5 mg/kg IV q8h) in synergistic combination with an antipseudomonal penicillin (eg, ticarcillin 4 g IV q4h or piperacillin 4 g IV q4h) or high-dose third-generation cephalosporin specific for gram-negative organisms (eg, ceftazidime 2 g IV q8h)
Intravenous drug use Initial therapy with vancomycin for methicillin-resistant S aureus, as well as single or combination therapy for Pseudomonas as listed for gram-negative bacilli
Tailor subsequent therapy based on culture results
Immunocompetent normal host
Initial therapy with IV vancomycin alone Tailor subsequent therapy based on culture
Chronically ill or immunocompromised
Initial therapy with broad coverage for gram-positive organisms (eg, vancomycin), gram-negative organisms, and anaerobes if clinically suspected; anaerobic coverage
can involve adding a -lactamase inhibitor to the antipseudomonal penicillin (eg, ticarcillin/clavulanate 3.1 g IV q4h or piperacillin/tazobactam 3.375 g IV q6h) or
adding metronidazole 500 mg IV q8h Tailor subsequent therapy based on culture results
Young adults with negative smear
Ceftriaxone 1 g IV q24h for suspected gonococcal infection
Neonates and children <2 months old
Broad-spectrum initial coverage for H influenzae (assume ampicillin resistance, so use a third-generation cephalosporin with the doses given above), S aureus (vancomycin as above if MRSA; nafcillin if MSSA), group B streptococci (best covered by penicillin, although sensitive to vancomycin, ceftriaxone, and ceftizoxime) and gram-negative bacilli
Combination of vancomycin, an extended-spectrum penicillin (eg, ticarcillin or piperacillin), and an aminoglycoside (eg, gentamicin or tobramycin) often used
Tailor subsequent therapy based on culture results
Mobilization
Management of septic arthritis also includes passive motion exercises to prevent formation of adhesions and to enhance the clearance of purulent exudates after the acute inflammatory response has subsided. Passive mobilization is gradually followed by active strengthening of periarticular structures to help prevent joint contractures.
Complications
The major complications of septic arthritis include osteomyelitis, persistent or recurrent infection, a marked decrease in joint mobility, ankylosis, or persistent pain.
Prognosis
The clinical outcome of septic arthritis is determined by the duration of symptoms before the initiation of effective treatment, the number of infected joints, the age and immune status of the patient, preceding joint disease, the virulence and susceptibilities of the organism, and the particular joint infected. Seventy to eighty-five percent of patients with group A streptococcal infections recover without residual symptoms. Up to 50% of patients with septic arthritis secondary to S aureus or gram-negative rods, however, have residual joint damage. Patients with RA and polyarticular infection have a guarded prognosis, with a survival rate <50%.
Chapter 98 – Arthritis Caused by Bacteria or Their Components GEORGE HO JR. SUE JOAN JUE PAUL PENISTON COOK
The normal diarthrodial joint is very resistant to bacterial infection because of local and systemic host defenses. However, bacteria can reach the synovial-lined joint via the hematogenous route and result in septic arthritis. The large joints are affected more commonly than the small joints, and monoarticular infection is the rule with polyarticular infection, more than one joint involved, in less than 20 percent of cases. A prospective series from a community-based population in the Netherlands reflected a representative distribution of joint involvement: knee 55 percent, ankle 10 percent, wrist 9 percent, shoulder 7 percent, hip 5 percent, elbow 5 percent, sternoclavicular, (SC) joint 5 percent, sacroiliac (SI) joint 2 percent, and foot joint 2 percent.[1]
Bacterial infections of the joint are curable with treatment, but the morbidity and mortality are still significant in patients with underlying rheumatoid arthritis (RA), patients with prosthetic joints, the elderly, and those who have severe and multiple comorbidities. Goldenberg wrote in 1994, "Treatment and outcome (of septic arthritis) have not improved substantially over the past 20 years."[2] This statement is probably still true today. However, incremental knowledge of the pathogenesis of septic arthritis caused by two common organisms, Neiserria gonorrhoeae and Staphylococcus aureus, and understanding the pathobiology of prosthetic devises may lead to innovations in the management and prevention of bacterial joint infections.
Epidemiology and Pathogenesis
The incidence of septic arthritis varies between 2 and 5 per 100,000 per year in the general population, 5.5 and 12 per 100,000 per year in children, 28 and 38 per 100,000 per year in patients with RA, and 40 and 68 per 100,000 per year in patients with joint prosthesis.[3][4] The organisms causing bacterial arthritis depend on the epidemiologic circumstances. For instance, monoarthritis of a prosthetic joint in an elderly man is likely due to Staphylococcus species, whereas a migratory arthritis in a sexually active woman with skin lesions is likely due to disseminated gonococcal infection.
Most cases of septic arthritis result from hematogenous seeding of the synovial membrane. The abundant vascular supply of the synovium, as well as the lack of a limiting basement membrane, allows organisms to target joints during bacteremia. Less common causes of septic arthritis include direct inoculation following joint aspiration or corticosteroid injection
of a joint[5]; animal or human bites; nail puncture wounds or plant thorn injury[6]; joint surgery, especially hip and knee arthroplasties; and spread by contiguous osteomyelitis, cellulitis, or septic bursitis. Arthrocentesis is a very common procedure frequently used in conjunction with corticosteroid administration in patients with various forms of joint diseases. Septic arthritis following joint aspiration and injection is extremely rare, occurring in 0.0002 percent of patients.[7] Arthroscopic surgery is also a common procedure that is complicated by a very low incidence of septic arthritis (less than 0.5% of procedures).[8][9] Staphylococcal species, coagulase positive and negative, account for more than 87 percent of these infections. Recently, the Centers for Disease Control (CDC) reported septic arthritis of the knee related to anterior cruciate ligament repair.[10] Cultures yielded gram-negative organisms, such as Pseudomonas aeruginosa, Citrobacter species, Klebsiella oxytoca, and mixed infection with S. aureus, Enterococcus faecalis, and P. aeruginosa. In these rare cases, the tissue allografts were identified as the source of the infection.
Acute bacterial arthritis is usually designated gonococcal or nongonococcal. In the case of gonococcal arthritis, N. gonorrhoeae possesses a variety of virulence factors on the cell surface. N. gonorrhoeae is able to attach to cell surfaces via filamentous outer-membrane appendages, or pili. Another outer membrane protein, Protein I, has forms IA and IB. Protein IA binds the host factor H and inactivates complement component, C3b, thereby circumventing the host's complement system.[11] Protein IA also prevents phagolysosomal fusion in neutrophils, thus enabling survival of the organism within the phagocytes. Lipooligosaccharide (LOS) is a gonococcal molecule similar to the lipopoly-saccharide (LPS) of other gram-negative bacteria and possesses endotoxin activity, which contributes to the joint damage seen in gonococcal arthritis.[12]
S. aureus is the most common organism causing non-gonococcal arthritis. The virulence of S. aureus is associated with its ability to attach to host tissue within the joint, evade host defenses, and cause damage to the joint. Some of these virulence factors and their mechanisms of action are listed in Table 98-1 . The attachment of S. aureus to the joint tissues is facilitated by microbial surface components recognizing adhesive matrix molecules (MSCRAMMs). MSCRAMMs are embedded in the cell wall peptidoglycan of S. aureus[13][14]
( Fig. 98-1 ). They bind to host matrix proteins, including collagen, fibrinogen, elastin, vitronectin, laminin, and fibronectin. Knockout gene experiments in animal models showed that the gene coding for the protein that binds collagen is an important virulence factor for S. aureus joint infections.[15] Most S. aureus isolates also express the fibronectin-binding proteins, FnbpA and FnbpB. Disruption of the respective genes, fnbpA and fnbpB, by knockout gene experiments completely obliterates adherence of S. aureus to fibronectin-coated surfaces (e.g., prosthetic joints).[16]
Table 98-1 -- VIRULENCE FACTORS OF STAPHYLOCOCCUS AUREUS AND THEIR MECHANISMS OF ACTION
Virulence Factor Mechanism of Action
Collagen-binding protein Binds collagen
Clumping factor A and B Binds fibrinogen
Fibronectin-binding protein A and B
Binds fibronectin
Capsular polysaccharide Antiphagocytic
Virulence Factor Mechanism of Action
Protein ABinds fragment crytallizable (Fc) portion of immunoglobulin G (IgG)
Toxic Shock Syndrome Toxin-1, (TSST-1)
Superantigen
Enterotoxins Superantigens
Figure 98-1 Schematic Diagram of Staphlococcus Aureus. Many of the cell-surface proteins are regulated by the agr locus (see text). At low cell concentrations, agr facilitates the production of the cell-surface proteins, which facilitate attachment to tissue. At higher cell concentrations, as occurs with establishment of infection, agr downregulates production of the cell-surface proteins and activates genes coding for exotoxins.
The genes of several S. aureus cell surface proteins (e.g., protein A, fibronectin-binding proteins, coagulase) and exotoxins (e.g., TSST-1, enterotoxin B, proteases, and hemolysins) are regulated by the accessory gene regulator agr.[17][18] At low cell numbers, such as at the time of infection, production of cell surface proteins for attachment to host tissues is facilitated by the agr gene. Once the cells have attached to tissue or an orthopedic device and have passed from exponential to stationary phase of growth, agr then represses the expression of genes coding for cell surface proteins and activates genes coding for exotoxins and tissue-destroying exoenzymes. Because of this complex effect on the different stages of infection, inhibitors of agr may reduce tissue destruction but actually enhance tissue colonization. This effect could have implications for chronic infections such as occur with prosthetic joints.
Adherence receptors may allow for the intracellular movement of S. aureus into host cells (e.g., osteoblasts, endothelial cells, and neutrophils).[19] Once internalized, the organism is protected from the host's immune system and from antimicrobial agents. Following adherence to the joint tissue, the bacteria activate the host immune response. Opsonization and phagocytosis are key defenses to eradicate the organism. S. aureus possesses two virulence factors, protein A and capsular polysaccharide, which interfere with these defenses. Protein A interferes with binding of complement by binding to the fragment crystallizable (Fc) portion of immunoglobulin G (IgG). The gene coding for protein A had been experimentally disrupted, and joint infection due to the altered strain in a mouse model resulted in less joint destruction than infection caused by the wild-type strain.[20] Capsular polysaccharide interferes with both opsonization and phagocytosis. Of the 11 reported capsule serotypes of S. aureus, types 5 and 8 account for up to 85 percent of clinical infections.[21] The capsule of these two serotypes is thinner, which facilitates the attachment to host fibronectin and fibrin.[22] Once attached to these host proteins, capsule production is upregulated to form a thicker capsule, which makes the bacteria more resistant to opsonization and phagocytosis. The thicker capsule is also able to conceal the highly immunogenic adherence proteins (MSCRAMMs).[23] A mutant of the type 5 capsule in a murine model had a lower rate of infection and resulted in less-severe arthritis compared to mice infected with the wild-type strain.[24] A vaccine consisting of type 5 and 8 polysaccharide reduced S. aureus bacteremia by more than half in 1804 hemodialysis
patients.[25] The duration of protection was approximately 40 weeks following a single vaccination.
S. aureus exotoxins (e.g., TSST-1 and enterotoxins) act as superantigens that bind to host major histocompatibility complex (MHC) class II molecules and T cell receptors (TCR), resulting in clonal expansion and activation of some T cells. This activation triggers the release of numerous cytokines, including interleukin-2 (IL-2), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α).[26] Upregulation of these cytokines results in systemic toxicity and joint damage. The stimulated T cells initially proliferate, but later disappear, likely due to apoptosis, and result in immunosuppression.[27] Internalized organisms that had been protected from this inflammatory response may then cause fulminant or persistent infection. Mice injected with strains of S. aureus lacking both TSST-1 and enterotoxins rarely develop arthritis; moreover, when arthritis is induced, it is much milder compared to animals injected with the wild-type strain.[26] Furthermore, vaccination of mice with a mutated, recombinant form of enterotoxin A devoid of superantigenicity was associated with a significant reduction in mortality.[28]
In response to bacterial infection of the joint space, the host releases a variety of cytokines and inflammatory mediators. Initially, IL-1β and IL-6 are released into the joint space, leading to an influx of inflammatory cells. These neutrophils and macrophages engulf invading bacteria and release additional cytokines, including TNF-α, IL-1, IL-6, and IL-8. Blocking TNF-α with a monoclonal antibody and IL-1 with an IL-1 receptor antagonist (IL-1Ra) inhibited leukocyte infiltration into the joint by 80 percent in a rabbit model of S. aureus-induced arthritis when the cytokine inhibitors were given simultaneously with S. aureus.[29] However, when the same inhibitors were given 24 hours following infection, there was no effect on leukocyte infiltration, suggesting the crucial roles of TNF-α and IL-1 in the early stages of S. aureus-induced arthritis. Release of IFN-γ is associated with the influx of T cells, which occurs a few days following infection. In a mouse model of S. aureus septic arthritis, IFN-γ has been associated with a worsening of the severity of arthritis, while, on the other hand, protecting the animals from septicemia.[30] Thus, the host's early cytokine response may aid the clearance of organisms and limit infection in the host. On the other hand, a late cytokine response may amplify the destructiveness of an established infection.
Acute bacterial arthritis is most commonly monoarticular. Polyarticular infection occurs in 5 to 8 percent of pediatric cases and in 10 to 19 percent of adult nongonococcal cases.[31][32] The differential diagnosis of acute monoarthritis overlaps with many causes of polyarthritis because virtually any arthritic disorder can initially present as a single swollen joint. The three main etiologies to consider when a patient presents with acute monoarticular arthritis are trauma, infection, and crystal-induced synovitis such as gout or pseudogout. Less commonly, systemic inflammatory disorders such as the spondyloarthropathies can present as acute monoarthritis. RA, systemic lupus erythematosus (SLE), and other connective tissue diseases are even less-common causes of monoarthritis.
Disseminated gonococcal infection (DGI) occurs in 1 to 3 percent of patients infected with N. gonorrhoeae. Gonococcal arthritis is the most common cause of acute monoarthritis in sexually active young adults. In the preantibiotic era, gonococcal arthritis was a well-recognized illness in neonates. DGI is three times more common in women than men. Patients with gonococcal joint disease typically present as one of two forms. The first is characterized by fever, shaking chills, vesiculopustular skin lesions, tenosynovitis, and polyarthralgias. Blood cultures are frequently positive, whereas synovial fluid cultures are rarely positive. N. gonorrhoeae can be cultured from genital, rectal, and pharyngeal sites. Tenosynovitis of multiple tendons of the wrist, fingers, ankle, and toes is a unique feature of this form of DGI and distinguishes it from other forms of infectious arthritis. In the other form of gonococcal infection, patients have purulent arthritis, most commonly of the knee, wrist, or ankle, and more than one joint can be infected simultaneously. N. gonorrhoeae can frequently be cultured from the synovial fluid.[33]
The classic presentation of nongonococcal septic arthritis is the acute onset of pain and swelling in a single joint. Large joints are affected most commonly. In adults, the knee is involved in more than 50 percent of cases, and hip, ankle, and shoulder infections are less common.[34] In infants and small children, hips are more often involved.[35] Patients with septic arthritis often have underlying illnesses and predispositions to infections. Many are immunocompromised, are intravenous (IV) drug abusers, have prosthetic joints, and have diseases such as neoplasia, renal failure, and RA. Table 98-2 lists the risk factors that predispose to septic arthritis.[3][5][36][37][38]
Table 98-2 -- RISK FACTORS FOR THE DEVELOPMENT OF SEPTIC ARTHRITIS
Age older than 80 years[3]
Diabetes mellitus[3]
Presence of a prosthetic joint in the knee or the hip[3]
Recent joint surgery[3]
Skin infection[3]
Previous septic arthritis[36]
Recent intra-articular injection[5]
Human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)
Intravenous (IV) drug abuse
End-stage renal disease on hemodialysis
Advanced hepatic disease
Hemophilia with or without AIDS
Sickle cell disease
Underlying malignancy
Hypogammaglobulinemia (susceptible to mycoplasma infections)[38]
Late complement-component deficiency (susceptible to neisserial infections)[37]
Low social economic status confounded by high rate of comorbidities[36]
Most patients with bacterial arthritis are febrile, although chills are unusual. Fever may be absent in the elderly. In children, septic arthritis is usually accompanied by fever, malaise, poor appetite, and irritability, as well as progressive reluctance to use the affected limb. Physical examination typically reveals warmth and tenderness of the affected joint, joint effusion, and limited active and passive range of motion. Septic arthritis among patients with RA has been a special challenge to clinicians because of the high incidence of infection and the poor outcome. Newer series of rheumatoid patients with septic arthritis are reported,[39] but they do not add new insights to the literature of a decade or more ago.[40][41][42][43] It is well recognized that septic arthritis in patients with RA is associated with poor joint outcome and mortality as high as 56 percent in those with polyarticular infection.[31] Does more aggressive drainage of an infected joint already damaged by rheumatoid disease result in a better outcome? How can the risk of infection in a host with RA be reduced and how can infection in a prosthetic joint of a rheumatoid patient be prevented? How can rheumatoid flare be differentiated from septic arthritis complicating rheumatoid disease? Whenever bacterial arthritis is suspected, the most important diagnostic procedure is arthrocentesis and examination of the synovial fluid. For those joints that are deep and more difficult to aspirate, ultrasound- or fluoroscopy-guided needle aspiration should be performed.
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Imaging
Plain radiographs in septic arthritis are usually normal early in the course of the infection, but baseline films should be obtained to look for evidence of other disease and contiguous osteomyelitis. Radiographs often demonstrate nonspecific changes of inflammatory arthritis, including periarticular osteopenia, joint effusion, soft tissue swelling, and joint-space loss. In more advanced infection, periosteal reaction, marginal or central erosions, and destruction of subchondral bone may be seen. Bony ankylosis is a late sequela of septic arthritis. Dislocation or subluxation of the femoral head is unique to hip infection of neonates.[35]
Ultrasound of the hip is the modality of choice to detect fluid collections in this deep joint and can serve as a guide in its aspiration. Ultrasound can be similarly used in other joints such as the popliteal cyst of the knee, shoulder, acromioclavicular (AC), or sternoclavicular Sternoclavicular, (SC), joints. Triple-phase bone scan using technetium-99 is often done in children to identify an associated metaphyseal osteomyelitis or avascular necrosis of the femoral head. Whole-body bone scan is preferred in young children because, despite focal symptoms, septic arthritis and ostemyelitis may be multifocal in this age-group.[75] In septic arthritis of all age-groups, the periarticular distribution of increased uptake is seen both on the early "blood-pool" phase and the delayed images of the joint. Bone scans, however, only provide nonspecific information and cannot differentiate septic from noninfectious causes of joint inflammation. Therefore, a suggestive bone scan must be interpreted in the proper clinical context and supported by microbiologic data for a definitive diagnosis of joint or bone infection.
In joints that are difficult to evaluate otherwise or that have complex anatomic structures, computed tomography (CT) and magnetic resonance imaging (MRI) can provide useful images to delineate the extent of the infection.[76] MRI is highly sensitive in early detection of joint fluid and is superior to CT in the delineation of soft tissue structures. These images can demonstrate early bone erosion, reveal soft tissue extension, and facilitate arthrocentesis of joints such as shoulders, hips, AC,[77] SC, and SI, as well as facet joints of the spine.
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Prognosis
In the 21st century, patients with septic arthritis as a group are becoming older, with more risk factors for infection and more comorbidities. The number of patients with prosthetic joints is increasing as the population of older patients grows and people live longer. Therefore, it is not surprising to see more cases of infection in total joint replacements. However, the organisms have not changed significantly. Staphylococci (44 to 66 percent) are still the dominant organism followed by streptococci (18 to 28 percent) and gramnegative bacilli (9 to 19 percent).[84] The emerging challenges in the treatment of septic arthritis are how to improve outcome, how to deal with resistant organisms, and how to overcome host factors that portend a poor prognosis.
The outcome of the treatment of septic arthritis can be measured as mortality, as the functional outcome of the infected joint, or as short-term and long-term outcomes. Certainly death from the infection is a poor outcome. Among the survivors, loss of articular cartilage, loss of motion, or increase in pain in the affected joint would be considered poor functional outcomes. Loss of the limb to infection or need for surgery to fuse the joint or restore function are also poor outcomes. Most studies report the outcome at the time of hospital discharge, and long-term data on adults with septic arthritis are not available. For example, the rate of development of degenerative joint disease, the rate of relapse or recurrence of infection, and the rate of progression of functional impairment in the affected joint over time have not been well studied.
Many retrospective studies have characterized features that may increase the chance of a poor outcome at the time of hospital discharge[36][42][64][85][86][87] ( Table 98-7 ). One prospective community-based study of adults and children found poor joint outcome in 33 percent of survivors among 154 patients with bacterial arthritis and noted older age, preexisting joint disease, and an infected joint containing synthetic material as negative prognostic factors by univariate analysis.[87] These investigators noted no association between poor outcome and young age, comorbidity, immunosuppressive medication, functional class, multiple infected joints, type of organism, or treatment delay.
Table 98-7 -- FACTORS THAT MAY PORTEND A POOR OUTCOME IN SEPTIC ARTHRITIS[36][42][64][85][86][87]
Older age
Preexisting arthritis, especially rheumatoid arthritis (RA) but also osteoarthritis (OA) and tophaceous gout
Presence of synthetic material (i.e., total joint replacement)
Delay in diagnosis or long duration of symptoms before seeking medical attention
Polyarticular infection, especially if more than three joints (four to nine) and small hand joints are affected
Presence of bacteremia
Infection caused by virulent or difficult to treat organisms (e.g., Staphylococcus aureus,
Pseudomonas aeruginosa or some gram-negative bacilli)
Patients receiving immunosuppressive therapy
Serious underlying comorbidities (e.g., liver, kidney, or heart diseases)
EpidemiologyPart of "6.2.2 - Pyogenic arthritis in children"Acute septic arthritis is a relatively uncommon infection. It is estimated that two of every 1000 admissions to general hospitals are for septic arthritis. In a 30-year study of paediatric skeletal infection reported by Nelson, 682 cases of suppurative arthritis were described with an occurrence of 25 cases among 10 000 annual admissions (Nelson 1991). Our institution serves a large, urban population in the American Midwest where approximately 10 000 children are admitted to the hospital each year. During the most recent 1 year evaluation there were 34 admissions for septic arthritis.Suppurative joint infection is an important disease of young children, with more than half of the cases occurring in children less than 3 years of age (Table 1). Although boys are reported to be affected twice as often as girls, in our series this predominance is seen most in the child older than 5 years; in the younger patient, the sex distribution tends to be more equal.Table 1 Suppurative joint infection. The Children's Mercy Hospital Kansas City
Age Total %
≤2 months 11 83–23 months 58 422–5 years 36 266–11 years 19 14>11 years 14 10
A history of non-penetrating trauma can be elicited in many children with septic arthritis; however, most investigators have questioned its role in the pathogenesis of the infection. In one study (Welkon et al. 1986), patients with septic arthritis and sterile cultures more frequently reported a history of trauma than those with culture-confirmed pyarthrosis.An antecedent infection of the upper respiratory tract frequently precedes septic arthritis due to H. influenzae type b and K. kingae compared with pyarthrosis due to S. aureus (Yagupsky et al. 1993).
ManagementPart of "6.2.2 - Pyogenic arthritis in children"The essentials of management of suppurative arthritis in childhood include the combination of an appropriately selected antimicrobial agent and adequate drainage of the pyarthrosis (see Box 1). Simple needle aspiration P.602
of the affected joint may be sufficient in some cases. However, emergency surgical drainage of the joint is mandatory in pyarthrosis of the hip and probably shoulder infection. Arthrotomy and drainage should also be considered in cases where the pus is thick, or when significant symptoms and signs persist despite initial needle aspiration of pus from the affected joint. Aggressive surgical management of Pseudomonas osteochondritis and septic arthritis following a nail puncture wound to the foot permits shortened antimicrobial therapy of only 7–10 days (Jacobs et al. 1989). An aminoglycoside plus ceftazidime are often used as initial therapy until susceptibility test results are available.Box 1 Management of suspected pyogenic arthritis in the child
Figure. No caption available.*Some patients are not candidates for home therapy. The decision may be based on clinical or microbiological features of diseases. There may be situations where therapy cannot be provided in a technically satisfactory manner.When a presumptive diagnosis of septic arthritis is made, parenteral antibiotics should be begun promptly. The choice of antimicrobial agents in the healthy child without a puncture
wound should be based on the age of the child and the suspected pathogen. Infants under 3 months of age should be treated initially with antimicrobial agents active against S. aureus, Gram-negative enteric organisms, and group B streptococcus. Children 3 months to 2 years of age should receive therapy active against S. aureus, S. pneumoniae (including penicillin-resistant strains), and K. kingae. Cefuroxime is appropriate initial coverage as long as concomitant meningitis is not present. Alternatively, a combination of an antistaphylococcal penicillin with a third-generation cephalosporin (usually cefotaxime or ceftriaxone) until the results of culture are known is reasonable. Use of an expanded spectrum agent such as meropenem, imipenem/cilastatin, or cefepime is another option; however, concerns over developing antimicrobial resistance precludes the routine prescribing of these drugs. In older children, an antistaphylococcal penicillin or cephalosporin is the drug of choice. Parenteral antimicrobial agents readily penetrate into infected joints, so intra-articular installation of antibiotics is not necessary.Drug resistanceCommunity-aquired methicillin-resistant S. aureus (MRSA) infections in children are becoming an increasing concern (Herold et al. 1998; Centers for Disease Control and Prevention 1999). Clinical infection caused by such P.603
strains are similar to those caused by methicillin-susceptible S. aureus. In contrast to hospital-acquired MRSA, community-acquired isolates are more likely to be susceptible to clindamycin which effectively penetrates bone and joint. The prevalence of community-acquired MRSA infection increased from 10/100 000 admissions to 208/100 000 admissions over the last decade. Established risk factors for MRSA infection were absent in one-half of such patients identified at a large Mid western urban facility. If rates continue to increase, clindamycin may be the first line agent for skeletal infections in the paediatric population (Hussain et al. 2000).Worldwide, S. pneumoniae isolates that are resistant to penicillin and cephalosporins have been increasingly recovered from patients with both systemic infections and infections of the upper respiratory tract. Risk factors for infection with a drug-resistant strain include daycare attendance and prior beta-lactam antibiotic therapy. Empiric therapy for septic arthritis due to suspected drug-resistant pneumococcus includes cefotaxime, ceftriaxone, clindamycin, or vancomycin. If vancomycin is administered, it should be discontinued as soon as antimicrobial susceptibility test results identify effective alternative agents (American Academy of Pediatrics 2000). Recently, conjugated pneumococcal vaccine was approved for infants beginning at two months of age. As use of this vaccine becomes more routine, the incidence of pneumococcal septic arthritis is expected to diminish significantly.Sequential intravenous–oral regimensThe efficacy of a sequential intravenous–oral antimicrobial regimen has been demonstrated by numerous prospective studies (e.g. Feigin et al. 1975; Jackson and Nelson 1982). Usually, intravenous therapy is given for 5 – 7 days. Because the CRP rapidly decreases with appropriate treatment of bacterial arthritis, it is a useful test to monitor the initial response to therapy. If the CRP remains high or increases again during treatment, it may indicate increased inflammation due to inadequate therapy or the need for surgical drainage of the joint (Kallio et al. 1997). After all surgical procedures and when there is definite clinical improvement, a patient may be considered for an oral regimen if (i) an appropriate oral antimicrobial is available, (ii) the patient is able to take and retain oral medication, and (iii) reliable follow-up is guaranteed. The need to test for bactericidal activity of serum samples is controversial and many experts do not use this assessment in the child who has a good clinical and laboratory response to treatment (Nelson 1997; Peltola et al. 1997).
The oral dosage of the selected antibiotic is two to three times that used for otitis media or skin and soft tissue infection. A peak serum bactericidal titre is sometimes used to monitor oral therapy. A serum specimen for blood levels is obtained 1 h after the oral dose is given (after the drug has reached steady-state concentrations) and adequate bactericidal activity should be confirmed. A serum bactericidal activity of at least 1 : 8 is considered adequate except in cases of streptococcal infection where a titre of 1 : 32 is needed. Adjustment of the antimicrobial dosage is usually required in 15 per cent of cases. In less than 5 per cent of cases, satisfactory bactericidal activity cannot be achieved and a total parenteral regimen must be used for the duration of therapy (Prober and Yeager 1979). Oral antibiotic regimens should not be used outside the hospital setting in a child unless adherence to therapy can be assured.The optimum duration of antimicrobial therapy for children with suppurative arthritis is dependent upon the duration of symptoms before diagnosis of the pathogen, the response to medical and surgical treatment, and whether or not there is concomitant bone infection. Generally, if the patient's clinical response is good and the ESR returns to normal, 3 weeks of therapy is adequate for staphylococcal and Gram-negative bacillary infection (Syrogiannopoulos and Nelson 1978). Shorter courses have been successful for streptococcal and haemophilus infection, in which a total of 10–14 days of therapy may be adequate. In all cases where an oral regimen is used, ESR should be monitored weekly until therapy is considered complete.The risk of relapse or recurrent disease is quite small in cases of primary joint infection; however, for the child with pyarthrosis and concomitant bone infection, the potential for relapse or sequelae is significant. Therefore, if adherence cannot be guaranteed, an oral regimen is not appropriate for such patients. Delayed diagnosis, delay in surgical drainage, slow clinical response, and undocumented compliance are all risk factors for chronic disease (Hallel and Salvati 1975).
