Curr Infect Dis Rep (2012) 14:558–565 DOI 10.1007/s11908-012-0285-1 SKIN, SOFT TISSUE, BONE, AND JOINT INFECTIONS (N SAFDAR, SECTION EDITOR) Septic Arthritis in the Native Joint Meghan B. Brennan & Jennifer L. Hsu Published online: 31 July 2012 # Springer Science+Business Media, LLC 2012 Abstract Septic arthritis of the native joint is an un- Introduction common infection but, when present, creates a signifi- cant risk for functional impairment of the affected joint Due to the potential for significant joint damage and mor- or, in severe cases, mortality. Knowledge of the most tality, septic arthritis (SA) is a medical emergency. The common pathogens, as well as appropriate diagnostics, incidence of acute SA of the native joint ranges from 2 to can facilitate earlier diagnosis and treatment, which, 10 cases per 100,000 individuals in the general population ideally, leads to improved long-term outcomes. In this [1]. Patients who are older, have underlying joint disease, or article, we discuss recent microbiologic trends and diag- are immunosuppressed experience higher rates. For exam- nostic tests, with an update on use of molecular testing. ple, populations with rheumatoid arthritis have incidence Empiric antibiotic regimens for native joint septic arthritis rates approaching 70 cases per 100,000 person-years [2]. are reviewed, as well as potential new therapies on the Clinicians may anticipate more cases of SA as the number of horizon. individuals in these high-risk categories increases. Delayed treatment of acute bacterial SA can lead to Keywords Septic arthritis . Infectious arthritis . irreparable joint destruction. Prompt diagnosis and appro- Osteoarticular infection . Hot swollen joint . Staphylococcus priate therapy can cure infection before such damage aureus . Arthrocentesis . Synovial fluid . White blood cell occurs. Optimally, this entails a pathogen-specific diagno- count . Culture . Polymerase chain reaction . Antibiotics . sis and tailored antimicrobial therapy. Definitive diagnosis Joint drainage . Dexamethasone . Bisphosphonates is challenging due to imperfect isolation of causative organisms. When presented with an acutely inflamed joint, clinicians often must make initial therapeutic decisions using incomplete data. M. B. Brennan Division of Infectious Disease, Epidemiology University of Wisconsin School of Medicine and Public Health, 1685 Highland Avenue, The exact incidence of SA is unknown for several reasons. Madison, WI 53705, USA First, it is an uncommon disease, making prospective studies e-mail: [email protected] challenging. Second, most reported series have restricted J. L. Hsu investigation to microbiologically confirmed cases meeting Sanford Health Infectious Disease, rigorous definitions, leading to underestimation of incidence 1205 South Grange Avenue, Suite 401, [3•]. Estimated incidence in the western hemisphere is 2–10 Sioux Falls, SD 57108, USA cases per 100,000 persons per year [1]. The incidence rises J. L. Hsu (*) in specific patient populations, including rheumatoid arthri- Department of Internal Medicine, Sanford School of Medicine of tis where annual incidence has been estimated at 70 cases the University of South Dakota, per 100,000 person-years [2]. Additional risk factors for SA 1400 West 22nd Street, Sioux Falls, SD 57105, USA include low socioeconomic status, male sex, previous joint e-mail: [email protected] pathology or surgery, diabetes mellitus, skin infection, Curr Infect Dis Rep (2012) 14:558–565 559 injection drug abuse, alcohol abuse, intra-articular cortico- structure with no basement membrane limiting bacterial ac- steroid injection, and possibly, human immunodeficiency cess to the joint space. Once in the joint, the low-shear fluid virus infection [4–7]. Overall, clinical experience suggests conditions allow for bacterial adherence and infection [18, that the incidence of SA is increasing secondary to rising 19]. Additionally, the production of host-derived extracellular numbers of older patients, immuncompromised patients, matrix proteins that aid in joint healing (e.g., fibronectin) may and orthopedic procedures. promote bacterial attachment [15]. Estimated mortality rates have varied from 4 % to 42 % Much of our current understanding regarding pathogen- [8•]. This wide range arises from variation in patient comor- esis comes from an experimental murine model of SA bidities and clinical presentation, since SA can present as mediated by S. aureus. Infection arises from a complex limited disease or part of a sepsis syndrome. One recent series interplay of host and bacterial factors. Tumor necrosis factor found an overall mortality rate of 16 % for methicillin- (TNF)-α and interleukins-1 and -10 are likely important in resistant S. aureus (MRSA) SA reported in the literature from mounting an effective immune response to S. aureus, while 1995 to 2010, which was comparable to 15 % reported by high levels of interleukin-4 might promote increased sus- Gupta et al. in 2003 [8•, 9]. In contrast, two prior series have ceptibility to SA [3•]. Data from animals also show that shown higher mortality rates with MRSA SA than with bacterial variability may explain the spectrum of severity methicillin-susceptible S. aureus (MSSA) infection [10, 11]. seen in human disease. For example, an S. aureus strain with There is also substantial morbidity with persistent joint dys- altered cell wall protein A results in less severe disease, while function occurring in up to 30 % [12•]. strains producing the virulence factor Panton-Valentine leukocidin cytotoxin have been associated with fulminant infection [3•]. Microbiology and Pathogenesis Staphylococci and streptococci are the most common caus- Clinical Presentation ative organisms in bacterial SA, accounting for 90 % of microbiologically proven infection (Table 1)[3•, 12•]. The Acute bacterial SA should be included in the differential increasing identification of MRSA correlates with the over- diagnosis of patients presenting with a hot, swollen joint all rise in MRSA infections [8•, 13, 14]. Gram-negative alone. Other considerations include crystalline arthritis, organisms are more common in older and immunocompro- rheumatic disease, and osteoarthritis. As part of the initial mised patients, while anaerobes are seen primarily in trauma, evaluation, physicians should inquire about associated diabetes mellitus, or injection drug use [15, 16•]. Haemophi- rashes, symptoms of tenosynovitis, recent arthroscopy, trau- lus influenzae was formerly an important pathogen; however, ma (including bites), intravenous drug use, sexual history, the incidence has significantly decreased with widespread and preceding travel. No specific clinical exam finding can vaccination [17]. distinguish between infectious and noninfectious arthritis. SA occurs after a pathogen enters the synovium through Pain and joint swelling are seen in 85 % and 78 %, respec- three potential routes: (1) hematogenous spread, (2) contigu- tively, of adults presenting with acute, monoarticular bacte- ous infection, and (3) direct inoculation through either trauma rial SA [20•]. About 50 % of patients present with fever, or an iatrogenic event. The synovium is a well-vascularized which is often not markedly elevated [20•, 21, 22]. There- fore, clinicians should not rule out SA on the basis of the absence of fever. Creating further confusion, fever is also a Table 1 Common bacteria causing septic arthritis common sign in patients with crystalline arthropathy [23]. In the absence of clear physical exam findings or symptoms, Gram-positive organisms Gram-negative Other organisms diagnostic tests are necessary to determine whether the joint is infected. S. aureus E. coli M. tuberculosis Streptococci P. mirabilis B. burgdorferi (S. pyogenes, S. pneumoniae) Diagnosis Coagulase-negative s P. aeruginosa taphylococci The Poor Diagnostic Utility of Blood Tests K. pneumoniae K. kingae Peripheral blood measurements of white blood cells (WBCs), Salmonella spp. erythrocyte sedimentation rate (ESR), or C-reactive protein N. gonorrhoeae, N. (CRP) have little diagnostic value. Multiple studies have meningitidis found no clinically meaningful difference between peripheral 560 Curr Infect Dis Rep (2012) 14:558–565 WBC counts in bacterial SA, as compared with crystalline arthritis or flares of rheumatic arthritis [20•, 24•, 25]. Many patients with SA have normal peripheral WBC counts, which limits the diagnostic utility. The positive likelihood ratio (LR) for a peripheral WBC count greater than 11 cells/mm3 is 1.7 (95 % CI 1.2, 2.3), and the negative LR is 0.46 (95 % CI 0.19, 1.1) [24•]. ESR is usually elevated in patients with acute SA. How- ever, it is also elevated in other arthritides [20•, 24•, 25]. While patients with SA may have a statistically significantly higher ESR than those with crystalline disease, the ranges broadly overlap [25]. Li and colleagues calculated the pos- Fig. 1 Approximate distribution of joint white blood cell counts (jWBC) in patients presenting with acute noninfectious and septic itive LR of an ESR greater than 20 mm/h as 0.84 (95 % CI arthritis. About half of patients with a jWBC of >50,000 cell/μL have 0.6, 1.2) and the negative LR as 2.4 (95 % CI 0.6, 7.4) [24•]. septic arthritis. However, half of septic arthritis patients present with Examination of CRP levels has resulted in similar findings. jWBCs below this threshold. The relative importance of this left-tailed Due to low specificity, CRP results do not significantly alter subset differs on