Septic Arthritis in Adults

Septic arthritis in adults Authors Don L Goldenberg, MD Daniel J Sexton, MD Section Editor Daniel J Sexton, MD Deputy Editor Elinor L Baron, MD, DTMH
Disclosures: Don L Goldenberg, MD Grant/Research/Clinical Trial Support: Pfizer (Fibromyalgia). Consultant/Advisory Boards: Pfizer; Lilly; Forest (Fibromyalgia). Daniel J Sexton, MD Consultant/Advisory Boards: Johnson & Johnson (surgical infections); National Football League (infection control and prevention). Elinor L Baron, MD, DTMH Employee of UpToDate, Inc. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy

All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Mar 2014. | This topic last updated: Aug 07, 2013. INTRODUCTION — The term septic arthritis usually refers to bacterial infection in a joint but also includes fungal and mycobacterial infections. Septic arthritis due to bacterial pathogens is often a dangerous and destructive form of acute arthritis. Predisposing factors, pathophysiology, clinical manifestations, diagnosis, and treatment of nongonococcal bacterial arthritis are reviewed here. Prosthetic joint infections, gonococcal arthritis, and fungal and mycobacterial arthritis are discussed separately because of their unique clinical manifestations. (See "Clinical manifestations and diagnosis of prosthetic joint infections" and "Treatment of prosthetic joint infections" and "Disseminated gonococcal infection" and "Skeletal tuberculosis".) PREVALENCE — The prevalence of bacterial arthritis among adults presenting with one or a few acutely painful joints has been estimated to range from 8 to 27 percent, the lower figure arises from a consecutive series of 100 patients presenting to an urban hospital emergency department; the latter figure is based on a study of 75 patients presenting emergently in Taiwan [1,2]. These series included some patients with prosthetic joints and a small minority in whom the final diagnosis was gonococcal septic arthritis. PREDISPOSING FACTORS — Predisposing factors for septic arthritis in adults were identified in a 2007 systematic review that included a total of 6242 patients with acutely painful joints [3]; 653 (10 percent) had septic arthritis. The predisposing factors and their predictive value (reflected by the estimated positive likelihood ratios [+LR]) are

summarized as follows [3,4]: ● Age greater than 80 years ● Diabetes mellitus ● Rheumatoid arthritis ● Prosthetic joint ● Recent joint surgery ● Skin infection, cutaneous ulcers ● IV drug abuse, alcoholism ● Previous intra-articular corticosteroid injection Each of these individual factors appears to have a modest impact on the risk of septic arthritis, however, combinations of independent risk factors substantially increase risk. As an example, acute joint pain in the presence of a joint prosthesis and concurrent evidence of skin infection is associated with a +LR of 15 (95% CI 8.1-28) [3]. (See "Glossary of common biostatistical and epidemiological terms", section on 'Likelihood ratio'.) Source of infection — Bacterial arthritis can result from a bite or other trauma, from direct inoculation of bacteria during joint surgery, or rarely it can occur when pre-existing bony infection adjacent to a joint extends through the cortex into the joint space. However, in most cases, bacterial arthritis arises from hematogenous spread to the joint [5-7]. A retrospective review, for example, evaluated 191 cases of septic arthritis: 72 percent were thought to have arisen hematogenously [7]. Common predisposing factors for hematogenous dissemination include injection drug use, indwelling catheters, and an underlying immunocompromised state such as HIV infection. Neonates and the elderly are at highest risk [8]. In some cases, bacterial arthritis is the presenting sign of infective endocarditis (IE) [9]. This is most likely to occur in patients who use illicit injection drugs. Endocarditis should also be suspected when septic arthritis due to Staphylococcus aureus, enterococci, or streptococci occurs in a patient without an obvious predisposing cause. (See "Clinical manifestations and diagnosis of infective endocarditis".)

Patients with hematogenously induced bacterial arthritis may present with joint abnormalities in the absence of signs of sepsis or bacteremia. These patients presumably acquired their infection from a transient or self-limiting bacteremia. It is unknown why only a small percentage of patients with bacteremia develop septic arthritis. For example, the incidence of pneumococcal septic arthritis in patients with pneumococcal bacteremia is extremely low (ranging from 0.5 to 0.7 percent in three different case series) [10]. Bacterial arthritis can occur in conjunction with bacterial meningitis. A prospective cohort study of 696 episodes of community-acquired bacterial meningitis in adults evaluated the presence of arthritis [11]. Arthritis was diagnosed in 48 or 696 (7 percent) of cases of meningitis. Joint fluid cultures were positive in 6 of 23 (26 percent) patients in whom aspiration was performed. Arthritis was most frequent in patients with meningococcal meningitis (12 percent). Bacterial arthritis can also occur by other mechanisms: ● Sternoclavicular joint arthritis is a rare complication of subclavian vein catheterization [12]. ● Septic arthritis of the hip can rarely result from femoral venipuncture or ruptured colonic diverticular disease in which the infection dissects retroperitoneal into the posterior thigh and hip joint, presenting as a seemingly spontaneous-onset polymicrobial septic arthritis [13,14]. HIV infection — Septic arthritis does not appear to occur more often in patients with HIV infection than in other patients [5]. However, patients with advanced HIV infection may develop septic arthritis due to a variety of opportunistic organisms, including fungi or mycobacteria [15], in addition to S. aureus [5]. Underlying arthritis — Bacteremia is more likely to localize in a joint with preexisting arthritis, particularly if associated with synovitis. As an example, a prospective community-based study of 154 patients with bacterial arthritis found that 40 percent had preexisting joint disease, usually either rheumatoid arthritis or osteoarthritis [16]. Patients with rheumatoid arthritis (RA) appear to be especially prone to bacterial arthritis but the risk may also be increased in gout, pseudogout, osteoarthritis, and Charcot's arthropathy [5,6]. Patients with RA may have additional predisposing factors, such as prior

intraarticular steroid injections, maintenance immunosuppressive medications, and anti-tumor necrosis factor (TNF) therapy [17-20]. (See "Tumor necrosis factor-alpha inhibitors and mycobacterial infections".) PATHOGENESIS — Bacteria entering the joint initially deposit in the synovial membrane and produce an acute inflammatory cell response. Because synovial tissue has no limiting basement plate, bacterial organisms may quickly gain access to the synovial fluid, characteristically creating acute-onset, purulent joint inflammation. Following the onset of infection, there is marked hyperplasia of the lining cells in the synovial membrane within seven days. In addition, inflammatory cells release cytokines and proteases that cause cartilage degradation and inhibit cartilage synthesis. Pressure necrosis from large synovial effusions may result in further cartilage and bone loss. Bacterial DNA and bacterial toxins may have a deleterious effect on joint structures. As an example, extracts of unmethylated bacterial DNA from S. aureus or Escherichia coli produced arthritis in a murine model that lasted up to 14 days [21]. Bacterial superantigens, such as staphylococcal toxic shock syndrome toxin (TSST)-1 and staphylococcal enterotoxins may induce a potent inflammatory response that damages joint cartilage. Animals infected with strains of S. aureus expressing TSST-1 and enterotoxin, for example, developed severe arthritis, while those infected with strains in which these toxins were absent had no or only mild joint inflammation. Moreover, vaccination with recombinant forms of staphylococcal enterotoxin protected mice against severe arthritis due to enterotoxin containing staphylococci [22]. (See "Staphylococcal toxic shock syndrome", section on 'pathogenesis'.) The presence of surface components on organisms such as S. aureus may be important in the pathogenesis of septic arthritis. Adhesins, called "microbial surface components recognizing adhesive matrix molecules" (MSCRAMMs), mediate adherence of staphylococci to intraarticular proteins, such as fibronectin, laminin, elastin, collagen, hyaluronic acid, and to prosthetic joint materials. There is increasing experimental and clinical evidence that the presence or absence of genes encoding certain MSCRAMMs affects whether or not individual strains of S. aureus cause septic arthritis [23]. A fibrinogen binding adhesion (FbsA) was a virulence factor in an animal model of septic arthritis following the intravenous injection of Streptococcus agalactiae [24]. In contrast, the absence of pili-mediated adherence factors in organisms such as Kingella kingae seem to be paradoxically associated with a tendency to develop joint, bone, or endocardial infections [25]. Microbiology — Many pathogens are capable of causing bacterial arthritis (table 1). S. aureus (including MRSA) is the most common bacterium infecting adult joints [4,6,26]. Other gram-positive organisms

such as streptococci are also frequent causes of septic arthritis. Septic arthritis due to gram-negative bacilli is generally observed in the setting of trauma, intravenous drug users, neonates, the elderly, and in association with underlying immunosuppression. Streptococcus pneumoniae cause a small but important percentage of cases of septic arthritis in adults. One review of 190 cases of pneumococcal septic arthritis noted that the majority of cases were monoarticular but that polyarticular involvement occurred in 36 percent [10]. Only one-half of the patients had another clinically apparent focus of pneumococcal infection. Septic arthritis is usually monomicrobial. Polymicrobial infections are less common and usually occur in the setting of penetrating trauma involving the joint space or via hematogenous seeding. CLINICAL MANIFESTATIONS — Patients with bacterial arthritis usually present acutely with a single swollen and painful joint (ie, monoarticular arthritis) [27]. The knee is involved in more than 50 percent of cases but wrists, ankles, and hips are commonly infected [5]. Infection of the symphysis pubis is uncommon but in a review of 100 cases four major underlying factors were identified including, patients who had undergone female incontinence surgery (24 percent), who were athletes (19 percent), who had pelvic malignancy (17 percent), or who used injection drugs (15 percent) [28]. (See "Pelvic osteomyelitis".) Approximately 20 percent of septic joint infections are oligoarticular or polyarticular, usually involving two or three joints. Polyarticular septic arthritis is most likely to occur in patients with RA or other systemic connective tissue disease and in patients with overwhelming sepsis [29]. Joint pain, swelling, warmth, and restricted movement are self-reported by a majority of patients. These symptoms were noted at presentation in 85 and 78 percent, respectively, of patients with septic arthritis [3]. A majority of patients with bacterial arthritis are febrile, although chills and spiking fevers are unusual [3]. Clinical experience suggests that elderly patients are more likely than others with septic arthritis to be afebrile. There may be evidence of an associated skin, urinary tract, or respiratory infection, which should provide a clue to the likely infecting organism (eg, S. aureus in patients presenting with skin and joint infections) (table 1). Injection drug users have a predilection to develop bacterial arthritis in axial joints, such as the sternoclavicular [30] or sternomanubrial joint. DIAGNOSIS — Bacterial arthritis is part of the differential diagnosis of acute monoarthritis (table 2). The definitive diagnostic test is

identification of bacteria in the synovial fluid. Thus, at the initial suspicion of joint infection, synovial fluid aspiration should be performed; Gram stain, culture, and leukocyte count and differential of the aspirated fluid often leads to the correct diagnosis (table 3 and algorithm 1). (See "Synovial fluid analysis".) The use of blood culture bottles for culture of synovial fluid may increase the rate of recovery of pathogens from patients with bacterial arthritis [31,32]. One study of 90 patients with acute joint effusions found no differences in the yield of positive cultures with the use of conventional agar plate culture, culture with lysis and centrifugation (Isolator) tubes, or broth enrichment blood culture bottles [33]. In patients with clinical signs of septic arthritis, joint fluid cultures were positive by all three methods in 8 patients and negative by all three methods in 19 patients. The contamination rate was 1.5 percent in patients without clinical evidence of septic arthritis. If synovial fluid cannot be obtained with closed needle aspiration, the joint should be aspirated under computed tomography (CT) or fluoroscopic or ultrasound guidance. Certain joints, such as the hip or sacroiliac joint, may require surgical arthrotomy for diagnostic aspiration. The following results are typically obtained from synovial fluid analysis in patients with bacterial arthritis [6]: ● Synovial fluid culture is positive in the majority of patients with nongonococcal bacterial arthritis. Negative cultures may occur in those who have received recent antimicrobial therapy or are infected with a fastidious organism such as some streptococci or mycoplasma. ● Gram stain is positive in many but not all cases. The sensitivity is estimated to be from 29-50 percent [3]. However, false positive results can be obtained because precipitated crystal violet and mucin in the synovial fluid can mimic gram-positive cocci. (See "Synovial fluid analysis".) ● The infected fluid is usually purulent with an average leukocyte count (most of which are neutrophils) of 50,000 to 150,000 cells/mm3. The likelihood of septic arthritis increases with rising synovial fluid leukocyte count [4].

● The synovial fluid glucose is often depressed and lactic acid concentration is elevated; however, these tests are not sufficiently sensitive to be of widespread diagnostic utility. Blood cultures are positive in approximately 50 percent of cases; thus, blood cultures should be obtained in any patient with suspected bacterial arthritis (even if fever is absent at the time of initial evaluation). Other laboratory findings, such as an increased white blood cell count and an elevated erythrocyte sedimentation rate, are common but nonspecific. Radiographs of the infected joint are usually normal at presentation but should be obtained in all patients since associated osteomyelitis or concurrent joint disease may rarely be present. In addition, a baseline radiograph is often useful for comparison purposes should the response to therapy be delayed or poor. Scintigraphy, CT scanning, or MR imaging can detect effusions and inflammation in joints that are difficult to examine, especially in the hip and sacroiliac joints [34]. Inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are commonly measured in the early evaluation of patients with septic arthritis; these significance of the levels of these markers in uncertain. Elevations of CRP are usually present, though the sensitivity of the ESR test in patients with septic arthritis is inconsistent [35,36]. DIFFERENTIAL DIAGNOSIS — The differential diagnosis of bacterial arthritis includes gout, pseudogout, reactive arthritis, RA, viral arthritis, and Lyme disease, each of which can present with acute involvement of one or a few joints (table 2). Crystal-induced arthritis — Crystal-induced arthritis is very difficult to differentiate from bacterial arthritis on clinical examination [37]. Patients with gout, for example, may have a monoarthritis with shaking chills, high fever, and leukocytosis. The diagnosis can be established by synovial fluid analysis, which should demonstrate the characteristic urate crystals of gout or the calcium pyrophosphate crystals of pseudogout. In addition, helpful clinical clues suggestive of gout include involvement of the first metatarsophalangeal joint, prior self-limited attacks of arthritis, and presence of tophi. Pseudogout may be more difficult to differentiate from a septic joint, since it often presents with acute knee or wrist synovitis. Radiographs demonstrating chondrocalcinosis are often helpful in this setting. (See "Clinical manifestations and diagnosis of calcium pyrophosphate crystal deposition disease".)

As some patients have concurrent crystal-induced and bacterial arthritis, we routinely culture and look for crystals in the synovial fluid from any joint with an acute effusion of unknown etiology. Reactive arthritis — Any form of chronic inflammatory joint disease can present with a new swollen joint that can simulate bacterial arthritis. This is especially common in the seronegative spondyloarthropathies, such as reactive arthritis. Most patients with reactive arthritis have recent genitourinary or gastrointestinal signs or symptoms, conjunctivitis, or skin or mucus membrane lesions. Occasionally patients with ankylosing spondylitis present with acute-onset hip arthritis that mimics septic arthritis [38]. (See "Reactive arthritis (formerly Reiter syndrome)".) Rheumatoid arthritis — Although rheumatoid arthritis (RA) is typically a symmetrical, chronic polyarthritis, an acute or subacute exacerbation of one or a few joints is common. It is important to differentiate such an exacerbation from concurrent bacterial arthritis. However, the correct diagnosis may be difficult to establish because the clinical findings may be somewhat atypical. As an example, many RA patients present indolently (rather than acutely) with bacterial arthritis, often with little fever or peripheral blood leukocytosis. Conversely, RA alone may present with a "pseudoseptic arthritis" picture, including an explosive acute synovitis with a marked synovial fluid leukocytosis [39]. Thus, Gram stain and culture of synovial fluid are essential when evaluating the new onset of synovitis in these patients. (See "Diagnosis and differential diagnosis of rheumatoid arthritis".) Lyme disease — Lyme disease can present with an acute monoarthritis. The arthritis may develop weeks or months after the characteristic rash, fever, and migratory arthralgias. Patients are generally from, or have visited, an endemic area and seasonal exposure is historically helpful. At the time of arthritis, almost all patients should have IgG antibodies to Borrelia burgdorferi, which should be confirmed by a more specific method such as Western blot. (See "Diagnosis of Lyme disease".) Other — Several other arthritides should be included in the differential diagnosis of bacterial arthritis. ● Mycobacterial and fungal [40,41] arthritis are much less common than bacterial arthritis, but have been seen more often in the context of HIV infection. An indolent monoarthritis is often the only symptom and synovial membrane histopathology and culture are frequently required to establish the diagnosis. (See "Skeletal tuberculosis", section on 'Arthritis'.)

● Gonococcal arthritis can present with an acute monoarthritis, although migratory polyarthritis and tenosynovitis are more typical. (See "Disseminated gonococcal infection".) ● An acute traumatic arthritis usually causes bloody synovial fluid and is generally associated with a history of significant trauma to the joint. ● Mycoplasma spp can cause arthritis that mimics many of the features of other forms of septic arthritis, particularly in patients with hypogammaglobulinemia. (See "Mycoplasma hominis and Ureaplasma urealyticum infections".) TREATMENT — Treatment of acute bacterial arthritis requires appropriate antimicrobials and adequate joint drainage (algorithm 2) [42]. Antibiotic therapy — No randomized controlled studies have evaluated antibiotic regimens for bacterial arthritis. The initial choice of antimicrobial regimens is based on coverage of the most likely organisms to cause infection in this setting, the Gram stain, the clinical presentation, and case series. ● If the initial Gram stain of the synovial fluid shows gram-positive cocci, we recommend treatment with vancomycin (15 to 20 mg/kg/dose every 8 to 12 hours, not to exceed 2 g per dose) [43]. ● If the initial Gram stain of the synovial fluid shows gram-negative bacilli, we recommend therapy be initiated with a third generation cephalosporin. Suggested antibiotics and regimens include: • Ceftazidime (1 to 2 g IV every eight hours) or • Ceftriaxone (2 g IV once daily) or

• Cefotaxime (2 g IV every eight hours)
 
 Ceftazidime should be given with an aminoglycoside such as gentamicin (3 to 5 mg/kg per day in two or three divided doses) when Pseudomonas aeruginosa is considered to be a likely pathogen (eg, in patients who inject illicit drugs). In cephalosporin-allergic patients, we suggest treatment with ciprofloxacin (400 mg IV every12 hours or 500 to 750 mg orally twice daily). ● If the initial Gram stain is negative, we treat with vancomycin in the immunocompetent patient and with vancomycin plus a third generation cephalosporin in the immunocompromised patient, in injection drug users [44] or in traumatic bacterial arthritis. Modifications of the initial regimen can be made to narrow coverage when the culture and susceptibility results are available. As an example, vancomycin should be discontinued in patients with staphylococcal or streptococcal infections that are susceptible to beta-lactam therapy. Septic arthritis due to MRSA should be treated with vancomycin; if this is not feasible due to allergy or drug intolerance, reasonable alternative agents include daptomycin (6 mg/kg/day IV), linezolid (600 mg PO or IV twice daily), or clindamycin (600 mg PO or IV three times daily) [43]. Intraarticular antibiotics — Intraarticular antibiotics are not recommended as effective parenteral or oral therapy produce adequate levels of antimicrobial agents in joint fluid. Furthermore, direct instillation of antibiotics into a joint may cause an inflammatory response [6]. Duration of therapy — There have been no controlled trials examining the duration of antimicrobial therapy in bacterial arthritis. Treatment recommendations are based on clinical case series and cannot be generalized for all patients. We typically give parenteral antibiotics for at least 14 days followed by oral therapy (if possible) for an additional 14 days. However, selected patients with infections due to organisms that are susceptible in vitro to oral agents with high bioavailability such as a fluoroquinolone can be successfully treated with a short course (four to seven days) of parenteral therapy followed by 14 to 21 days of oral therapy. Compliance and response to therapy should be monitored carefully in all such patients. Longer courses of parenteral antimicrobial therapy (eg, three to four weeks) may be necessary to cure selected patients with difficult to treat pathogens such as P. aeruginosa or Enterobacter spp. Furthermore, we routinely advise a four week course of therapy in patients who have

documented bacteremia and secondary S. aureus arthritis; a shorter duration of therapy in such patients is likely to result in relapse. Joint drainage — No randomized controlled studies have evaluated joint drainage procedures in adults for bacterial arthritis. Thus, recommendations are based on small retrospective studies and are dependent on the joint affected and the time from onset of infection until evaluation. Although no studies have compared drainage to no drainage procedure, we recommend joint drainage in all patients with septic arthritis as this condition represents a closed abscess collection. The three procedures used are needle aspiration (single or multiple), arthroscopic drainage, or arthrotomy (open surgical drainage). Most peripheral joints can be drained with closed needle aspiration; daily aspiration may be necessary [45]. If adequate drainage cannot be obtained by needle aspiration, either arthroscopy or open drainage is necessary. Adequacy of needle aspiration is best assessed using clinical criteria, including improvement in temperature, white cell count, joint swelling and pain. Improvement in joint swelling is easier to assess in the knee than in the hip or shoulder. In most cases, initial surgical drainage is warranted for hips, shoulders, or prosthetic joint infections. Surgical drainage should also be undertaken for any joint that is not improving clinically after serial needle aspiration or if needle drainage is inadequate to remove the fluid [5,6]. For knee, shoulder, and wrist infections, arthroscopy is often preferred because of easier irrigation and better visualization of the joint [46-48]. A multicenter study of 46 cases of septic arthritis of the knee treated by arthroscopic drainage showed a bacteriologic cure rate of 78 percent [46]. A retrospective study of 76 patients with septic arthritis (62 knee, 10 shoulder, five ankle joints, and one hip joint) evaluated initial arthroscopic management [47]. Outcomes were dependent on the stage of infection, with more severe infections more likely to require repeated arthroscopic irrigations. For hip infections, initial open surgical drainage may be necessary. Although arthrotomy has been considered standard treatment, a retrospective study involving six patients with septic hips found that arthroscopic treatment with large-volume irrigation was effective [49]. Further clinical studies will be needed to determine the best approach. After initial treatment, serial synovial fluid analyses should demonstrate that the fluid has become sterile and that the total leukocyte count is decreasing. If not, more definitive joint drainage and/or an alteration in the antimicrobial regimen should be considered. Infected knees often continue to accumulate synovial fluid and require daily aspiration for 7

to 10 days. Attention should also be paid to joint position and rapid mobilization to prevent contractures and promote optimal nutrition to the articular cartilage. PROGNOSIS — The prognosis of bacterial arthritis has not improved significantly in the past few decades, despite better antibiotics and drainage. It is extremely difficult to predict the functional outcome of individual patients during and at the conclusion of treatment. The outcome is directly related to host factors, such as prior joint damage, the virulence of the infecting organism, and the speed with which adequate treatment is begun. As an example, a study evaluated 121 adults and 31 children with bacterial arthritis [16]. A poor joint outcome (as defined by the need for amputation, arthrodesis, prosthetic surgery or severe functional deterioration) occurred in one-third of the patients. Adverse prognostic factors included older age, preexisting joint disease, and an infected joint containing synthetic material. In addition, inflammation and destruction of joints may continue even in those with sterile joints despite effective antimicrobial therapy [50]. This may be due to the persistence of bacterial DNA within the joint, which has been shown to induce arthritis in an animal model of septic arthritis [21]. The pathogen may also have an important influence on the outcome of treatment. In the series of patients with pneumococcal bacterial arthritis, for example, 95 percent of adults and 90 percent of children had a return to baseline joint function or only mild limitation of joint motion following the completion of therapy [10]. These results are in contrast to other studies of S. aureus bacterial arthritis that report 46 to 50 percent with poor joint outcomes following therapy [6,51]. Mortality due to bacterial arthritis is dependent upon the presence of comorbid conditions such as advanced age, coexistent renal or cardiac disease, and immunosuppression. The mortality rates in most series have ranged from 10 to 15 percent [16]. Polyarticular septic arthritis, particularly when it is due to S. aureus or occurs in the presence of rheumatoid arthritis, has an extremely poor prognosis with mortality rates as high as 50 percent [29]. Mortality due to septic pneumococcal arthritis was reported as 19 percent in one series [10]. 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 5th to 6th 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 10th to 12th 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 e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.) ● Basics topic (see "Patient information: Septic arthritis (The Basics)") ● Beyond the Basics topics (see "Patient information: Arthritis (Beyond the Basics)" and "Patient information: Joint infection (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS ● Nongonococcal bacterial arthritis is frequently a dangerous and destructive form of acute arthritis. Bacterial arthritis can result from a bite or other trauma, from direct inoculation of bacteria during joint surgery, or rarely, when infection of bone adjacent to the joint extends through the cortex into the joint space. However, in most cases, bacterial arthritis arises from hematogenous spread to the joint. (See 'Introduction' above and 'Predisposing factors' above.) ● Bacteremia is more likely to localize in a joint with preexisting arthritis, particularly if associated with synovitis. Thus, patients with rheumatoid arthritis (RA) appear to be especially prone to bacterial arthritis but the risk is also increased in gout, pseudogout, osteoarthritis, and Charcot's arthropathy. (See 'Underlying arthritis' above.) ● Virtually any microbial pathogen is capable of causing bacterial arthritis. However, organisms such as S. aureus and streptococci

have a higher propensity to cause joint infections than gramnegative bacilli, which typically only produce these infections after trauma or in patients with severe underlying immunosuppression. (See 'Microbiology' above.) ● Patients with bacterial (nongonococcal) arthritis present acutely with a single swollen and painful joint (ie, monoarticular arthritis). The knee is involved in more than 50 percent of cases but wrists, ankles, and hips are commonly infected. (See 'Clinical manifestations' above.) ● Bacterial arthritis is part of the differential diagnosis of acute monoarthritis (table 2). (See 'Differential diagnosis' above.) ● The definitive diagnostic test is identification of bacteria in the synovial fluid. Thus, at the initial suspicion of joint infection, synovial fluid aspiration should be performed; Gram stain, culture, and leukocyte count and differential of the aspirated fluid often leads to the correct diagnosis (table 3 and algorithm 1). (See 'Diagnosis' above.) ● We recommend that the initial choice of antibiotics for treatment of acute nontraumatic bacterial arthritis be based on the Gram stain (Grade 1B). (See 'Antibiotic therapy' above.) ● We recommend that if the bacterial arthritis is due to trauma, or if the Gram stain is negative, the initial choice of antibiotics for treatment be based on coverage of the most likely organisms to cause infection in the clinical setting (Grade 1C). ● Typical antibiotic regimens include: • If the initial Gram stain of the synovial fluid shows grampositive cocci, we treat with vancomycin (15 to 20

mg/kg/dose every 8 to 12 hours, not to exceed 2 g per dose). • If the initial Gram stain of the synovial fluid shows gramnegative bacilli, we treat with a third generation cephalosporin, such as:
 
 Ceftazidime (1 to 2 g IV every eight hours) or ceftriaxone (2 g IV once daily) or cefotaxime (2 g IV every eight hours). • When Pseudomonas aeruginosa is considered to be a likely pathogen (eg, in patients who inject illicit drugs), we treat with ceftazidime and an aminoglycoside such as gentamicin (3 to 5 mg/kg per day in two or three divided doses). • In cephalosporin-allergic patients, we treat with ciprofloxacin (400 mg IV every12 hours or 500 to 750 mg orally twice daily). ● If the initial Gram stain is negative, we treat with vancomycin in the immunocompetent patient and with vancomycin plus a third generation cephalosporin in the immunocompromised patient or in traumatic bacterial arthritis. (See 'Antibiotic therapy' above.) ● Modifications of the initial antibiotic regimen should be made to narrow coverage when the culture and susceptibility results are available. (See 'Antibiotic therapy' above.) ● The typical duration of therapy is three to four weeks combined intravenous (approximately two weeks) and oral. (See 'Duration of therapy' above.) ● We recommend joint drainage be performed in all patients with bacterial arthritis (Grade 1C) (algorithm 2). (See 'Joint drainage' above.)

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1.Shmerling RH, Delbanco TL, Tosteson AN, Trentham DE. Synovial fluid tests. What should be ordered? JAMA 1990; 264:1009. 2.Jeng GW, Wang CR, Liu ST, et al. Measurement of synovial tumor necrosis factor-alpha in diagnosing emergency patients with bacterial arthritis. Am J Emerg Med 1997; 15:626. 3.Margaretten ME, Kohlwes J, Moore D, Bent S. Does this adult patient have septic arthritis? JAMA 2007; 297:1478. 4.Mathews CJ, Coakley G. Septic arthritis: current diagnostic and therapeutic algorithm. Curr Opin Rheumatol 2008; 20:457. 5.Goldenberg DL. Septic arthritis and other infections of rheumatologic significance. Rheum Dis Clin North Am 1991; 17:149. 6.Goldenberg DL, Reed JI. Bacterial arthritis. N Engl J Med 1985; 312:764. 7.Morgan DS, Fisher D, Merianos A, Currie BJ. An 18 year clinical review of septic arthritis from tropical Australia. Epidemiol Infect 1996; 117:423. 8.Gavet F, Tournadre A, Soubrier M, et al. Septic arthritis in patients aged 80 and older: a comparison with younger adults. J Am Geriatr Soc 2005; 53:1210. 9.Sapico FL, Liquete JA, Sarma RJ. Bone and joint infections in patients with infective endocarditis: review of a 4-year experience. Clin Infect Dis 1996; 22:783. 10. Ross JJ, Saltzman CL, Carling P, Shapiro DS. Pneumococcal septic arthritis: review of 190 cases. Clin Infect Dis 2003; 36:319. 11. Weisfelt M, van de Beek D, Spanjaard L, de Gans J. Arthritis in adults with community-acquired bacterial meningitis: a prospective cohort study. BMC Infect Dis 2006; 6:64. 12. Aglas F, Gretler J, Rainer F, Krejs GJ. Sternoclavicular septic arthritis: a rare but serious complication of subclavian venous catheterization. Clin Rheumatol 1994; 13:507. 13. Fromm SE, Toohey JS. Septic arthritis of the hip in an adult following repeated femoral venipuncture. Orthopedics 1996; 19:1047. 14. Messieh M, Turner R, Bunch F, Camer S. Hip sepsis from retroperitoneal rupture of diverticular disease. Orthop Rev 1993; 22:597. 15. Reveille JD. The changing spectrum of rheumatic disease in human immunodeficiency virus infection. Semin Arthritis Rheum 2000; 30:147. 16. Kaandorp CJ, Krijnen P, Moens HJ, et al. The outcome of bacterial arthritis: a prospective community-based study. Arthritis

17.

18.

19.

20.

21. 22.

23. 24.

25.

26. 27. 28. 29. 30. 31.

32.

33.

Rheum 1997; 40:884. Mor A, Mitnick HJ, Greene JB, et al. Relapsing oligoarticular septic arthritis during etanercept treatment of rheumatoid arthritis. J Clin Rheumatol 2006; 12:87. Nadarajah K, Pritchard C. Listeria monocytogenes septic arthritis in a patient treated with etanercept for rheumatoid arthritis. J Clin Rheumatol 2005; 11:120. Schett G, Herak P, Graninger W, et al. Listeria-associated arthritis in a patient undergoing etanercept therapy: case report and review of the literature. J Clin Microbiol 2005; 43:2537. Katsarolis I, Tsiodras S, Panagopoulos P, et al. Septic arthritis due to Salmonella enteritidis associated with infliximab use. Scand J Infect Dis 2005; 37:304. Deng GM, Tarkowski A. The features of arthritis induced by CpG motifs in bacterial DNA. Arthritis Rheum 2000; 43:356. Nilsson IM, Verdrengh M, Ulrich RG, et al. Protection against Staphylococcus aureus sepsis by vaccination with recombinant staphylococcal enterotoxin A devoid of superantigenicity. J Infect Dis 1999; 180:1370. Shirtliff ME, Mader JT. Acute septic arthritis. Clin Microbiol Rev 2002; 15:527. Jonsson IM, Pietrocola G, Speziale P, et al. Role of fibrinogenbinding adhesin expression in septic arthritis and septicemia caused by Streptococcus agalactiae. J Infect Dis 2005; 192:1456. Kehl-Fie TE, Porsch EA, Yagupsky P, et al. Examination of type IV pilus expression and pilus-associated phenotypes in Kingella kingae clinical isolates. Infect Immun 2010; 78:1692. Frazee BW, Fee C, Lambert L. How common is MRSA in adult septic arthritis? Ann Emerg Med 2009; 54:695. Mikhail IS, Alarcón GS. Nongonococcal bacterial arthritis. Rheum Dis Clin North Am 1993; 19:311. Ross JJ, Hu LT. Septic arthritis of the pubic symphysis: review of 100 cases. Medicine (Baltimore) 2003; 82:340. Dubost JJ, Fis I, Denis P, et al. Polyarticular septic arthritis. Medicine (Baltimore) 1993; 72:296. Ross JJ, Shamsuddin H. Sternoclavicular septic arthritis: review of 180 cases. Medicine (Baltimore) 2004; 83:139. von Essen R, Hölttä A. Improved method of isolating bacteria from joint fluids by the use of blood culture bottles. Ann Rheum Dis 1986; 45:454. Baron EJ, Miller JM, Weinstein MP, et al. A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2013 recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)(a). Clin Infect Dis 2013; 57:e22. Kortekangas P, Aro HT, Lehtonen OP. Synovial fluid culture and

34. 35. 36.

37. 38.

39.

40.

41. 42. 43.

44.

45. 46. 47.

48.

49. 50.

blood culture in acute arthritis. A multi-case report of 90 patients. Scand J Rheumatol 1995; 24:44. Zimmermann B 3rd, Mikolich DJ, Lally EV. Septic sacroiliitis. Semin Arthritis Rheum 1996; 26:592. Ernst AA, Weiss SJ, Tracy LA, Weiss NR. Usefulness of CRP and ESR in predicting septic joints. South Med J 2010; 103:522. Hariharan P, Kabrhel C. Sensitivity of erythrocyte sedimentation rate and C-reactive protein for the exclusion of septic arthritis in emergency department patients. J Emerg Med 2011; 40:428. Baker DG, Schumacher HR Jr. Acute monoarthritis. N Engl J Med 1993; 329:1013. Mathur T, Manadan AM, Hota B, Block JA. Pseudo-septic hip arthritis as the presenting symptom of ankylosing spondylitis: a case series and review of the literature. Clin Exp Rheumatol 2010; 28:416. Singleton JD, West SG, Nordstrom DM. "Pseudoseptic" arthritis complicating rheumatoid arthritis: a report of six cases. J Rheumatol 1991; 18:1319. Yang SC, Shao PL, Hsueh PR, et al. Successful treatment of Candida tropicalis arthritis, osteomyelitis and costochondritis with caspofungin and fluconazole in a recipient of bone marrow transplantation. Acta Paediatr 2006; 95:629. Dalton PA, Munckhof WJ, Walters DW. Scedosporium prolificans: an uncommon cause of septic arthritis. ANZ J Surg 2006; 76:661. Sharff KA, Richards EP, Townes JM. Clinical management of septic arthritis. Curr Rheumatol Rep 2013; 15:332. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52:e18. Allison DC, Holtom PD, Patzakis MJ, Zalavras CG. Microbiology of bone and joint infections in injecting drug abusers. Clin Orthop Relat Res 2010; 468:2107. Ho G Jr. How best to drain an infected joint. Will we ever know for certain? J Rheumatol 1993; 20:2001. Thiery JA. Arthroscopic drainage in septic arthritides of the knee: a multicenter study. Arthroscopy 1989; 5:65. Stutz G, Kuster MS, Kleinstück F, Gächter A. Arthroscopic management of septic arthritis: stages of infection and results. Knee Surg Sports Traumatol Arthrosc 2000; 8:270. Sammer DM, Shin AY. Comparison of arthroscopic and open treatment of septic arthritis of the wrist. J Bone Joint Surg Am 2009; 91:1387. Nusem I, Jabur MK, Playford EG. Arthroscopic treatment of septic arthritis of the hip. Arthroscopy 2006; 22:902.e1. Goldenberg DL. Septic arthritis. Lancet 1998; 351:197.

51.

Weston VC, Jones AC, Bradbury N, et al. Clinical features and outcome of septic arthritis in a single UK Health District 19821991. Ann Rheum Dis 1999; 58:214. Topic 7666 Version 14.0