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Home , Septic arthritis

Curr Infect Dis Rep (2012) 14:558–565 DOI 10.1007/s11908-012-0285-1

SKIN, SOFT TISSUE, , AND (N SAFDAR, SECTION EDITOR)

Septic 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 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 , 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 have incidence Empiric 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 . priate therapy can cure infection before such damage aureus . . . occurs. Optimally, this entails a -specific diagno- count . Culture . Polymerase chain reaction . . 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 , 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 cess to the joint space. Once in the joint, the low-shear fluid 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 syndrome. One recent series interplay of host and bacterial factors. found an overall 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 . 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 , recent , 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 , 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 causing septic arthritis common sign in patients with crystalline [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. Streptococci P. mirabilis B. burgdorferi (S. pyogenes, S. pneumoniae) Diagnosis -negative s P. aeruginosa taphylococci The Poor Diagnostic Utility of Blood Tests K. pneumoniae K. kingae Peripheral blood measurements of white blood cells (WBCs), 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 the basis of whether the reference group is all patients with septic arthritis or all patients with jWBCs of <50,000 cell/μL the pretest probability of SA [20•, 25]. Inflammatory markers may be better used in conjunction with synovial fluid analysis. If peripheral WBC and ESR are normal and if therapy can be made. Additionally, crystals in joint fluid do the synovial WBC is less than 20,000, Li and colleagues not exclude infection, given the potential for concomitant calculated a negative likelihood ratio of 0 (95 % CI 0, 13) SA [30]. [24•]. The confidence interval is wide due to the low number Joint WBCs are most difficult to interpret when they lie of subjects, limiting the utility of these findings. Efforts to between 2,000 and 50,000 cells/μL. Two comparisons arise: replicate this finding in a larger study could improve diag- (1) the proportion of people with SA with jWBCs of <50,000 nostic algorithms. cells/μL and (2) the proportion of people with jWBCs of While most blood tests offer little diagnostic aid, blood <50,000 cells/μL who have SA. These ratios outline the cultures can provide critical information. They should al- relative importance of SA patients in the left tail (low jWBCs) ways be drawn when considering the diagnosis of SA— (Fig. 1). If suspicion for SA is high, clinicians are interested in preferably, prior to antimicrobial initiation. Weston et al. how many patients with SA have jWBCs of <50,000 cells/μL. reported that 25 % of patients with SA were bacteremic, Roughly half of patients with SA will have jWBCs below this and in 9 % of cases, blood cultures provided the only threshold. One series found positive joint cultures in 19/49 microbiologic evidence of infection [21]. If the patient is (39 %) patients who had jWBCs of <50,000 cells/μL(95%CI found to have joint and positive blood cul- 25, 52) [27]. They estimated 60 % sensitivity (95 % CI 48, tures, SA should be diagnosed on the basis of the likelihood 75). Simply lowering this threshold slightly would not signif- of hematogenous seeding. icantly increase the sensitivity, since the left tail is spread over a wide range of lower values (Fig. 1). The specific pathogen The Importance of Arthrocentesis may play a role in the degree of jWBC elevation. Pyogenic infections such as S. aureus may lead to higher jWBCs, Arthrocentesis should always be performed when SA is while gonococcal, mycobacterial, and other atypical infec- suspected. Fluid should be sent routinely for cell count, tions may manifest with lower cell counts [26•]. To date, , bacterial culture, and microscopic exam for no study has been large enough to conduct a properly crystals. The joint WBC count (jWBC) has often been used powered subgroup analysis based on causative agents. To to help distinguish SA from noninfectious arthritis. However, summarize, if a clinician has a high pretest probability of defining a specific cutoff has been challenging, due to differ- SA but the jWBC is <50,000 cells/μL, he or she should ing distributions of the jWBC in these two disease categories consider empiric antibiotic therapy. (Fig. 1). Finding greater than 50,000 cells/μL has traditionally When there is a low clinical suspicion for SA, the clinician identified patients with infection. As the jWBC increases, so is interested in the number of patients with jWBCs of <50,000 does the likelihood of SA, with the LR for a jWBC greater cells/μL who have SA. Coutlakis et al. conducted a review of than 50,000 cells/μL reported as 7.7 (95 % CI 5.7, 11) [20•]. 202 consecutive patients whose synovial fluid studies includ- Over half of patients in this group will be diagnosed with SA, ed a WBC greater than 2,000 [26•]. Among 172 patients and 40 %–70 % of patients with SA will have jWBCs above whose jWBC was <50,000 cells/μL, only 9 (5 %) had SA. this threshold [26•, 27–29]. Therefore, when the jWBC is Overall, the study included a total of 27 patients with SA. greater than 50,000 cells/μL, a clear case for empiric antibiotic Therefore, although one third of the patients with infections Curr Infect Dis Rep (2012) 14:558–565 561 had a jWBC below 50,000 cells/μL, only 5 % of patients with The Prospect of 16S rDNA PCR a jWBC between 2,000 and 50,000 cells/μLhadSA. The jWBC should be considered in conjunction with In the absence of a positive synovial fluid culture, the other laboratory values when assessing patients. As has been diagnosis of SA rests on an accumulation of evidence. An mentioned, combining jWBC with peripheral blood tests optimal diagnostic test would be rapidly available with may have some negative predictive utility. Another impor- high sensitivity and pathogen-specific information to tant combination may be the jWBC and Gram stain results, guide microbial therapy. In the acute setting, a high neg- both of which are typically rapid tests. Approximately half ative predictive value would also be very valuable, since it of the patients with SA have a positive Gram stain [21, 27]. could rule out SA and reduce the need for empiric anti- However, one study reported that 15/49 (30 %) of patients microbials. Molecular techniques may provide a faster diagnosed with SA by culture had both a negative Gram method for diagnosis [35, 36]. 16S ribosomal polymerase stain and a jWBC of <50,000 cells/μL[27]. Data on all chain reaction (PCR) is based on amplification of relative- types of patients with synovial fluid analysis, not just those ly conserved regions of bacterial ribosomal DNA. Then, who were diagnosed with SA, are needed to calculate the amplicons can be identified by sequencing species-specific negative LR of a jWBC of <50,000 cells/μL coupled with a probes, or hybridization. This technique has been useful in negative Gram stain. other infections—especially, , ophthalmitis, and . Optimizing Synovial Fluid Culture Results In a small study of 18 patients without prosthetic evaluated for possible SA (26 synovial fluid samples), 16S The proportion of patients diagnosed with SA who have rDNA PCR followed by sequencing of positive results positive synovial fluid cultures varies greatly, from 30 % yielded a sensitivity of 73 % and a specificity of 95 %, as to 90 % [31, 32]. Performing arthrocentesis prior to antibi- compared with the physician’s final diagnosis [37]. The otic administration likely has the most important effect on negative predictive value was 0.875; all but one sample culture positivity. Processing synovial fluid specimens using was positive by culture. As compared with the physician’s pediatric technology rather than agar plates final diagnosis, culture was 97 % sensitive and 86 % spe- may further enhance yield [32, 33]. Pediatric tubes should cific. There was full agreement between culture results and be used, since most synovial fluid samples are low volume. PCR results regarding species identification. This study was There are many theoretical advantages to using blood cul- hampered by its small sample size and enrollment of only ture systems [34]. First, the pathogen concentration is low in patients with high clinical suspicion for SA. Fenollar and synovial fluid. By culturing an increased volume of fluid, colleagues conducted a larger, prospective analysis compar- the blood culture system is able to increase the probability ing 16S rDNA PCR followed by sequencing [38•]. Five of a positive result. Second, many naturally occurring hundred twenty-five bone and joint cultures were taken inhibitors, as well as previously administered antibiotics, from an equal number of patients and processed in parallel, can be neutralized or diluted in blood culture bottles. comparing PCR and sequencing with standard agar culture. Third, phagocytes in synovial fluid may harbor bacteria The molecular technique had a sensitivity of 92 % and a in their vacuoles. When lysed, culture of these intracellular specificity of 96 %, as compared with a culture sensitivity of organisms is possible. 87 % and a specificity of 89 %. The negative predictive In practice, single-institution studies indicate that blood value of rDNA PCR was 98 %. Congruent results using both culture systems are more sensitive than agar plates. One methods were seen in 475 samples (89 positive samples and study comparing 805 synovial fluid samples processed in 386 negative samples). In 21 cases, the PCR result was tandem, using the standard agar plate method (sheep’s blood positive, but culture was negative. Antibiotic suppression and chocolate agar) and a pediatric BACTEC blood culture likely inhibited growth in 7 of these, highlighting the impor- system, reported 62 positive cultures (Becton Dickinson tance of performing arthrocentesis prior to administration of Diagnostic Instrument Systems, Sparks, MD) [34]. Of these, antibiotics. 51 were detected using both methods, while 11 (18 %) were PCR results are usually available in a matter of hours detected using the blood culture system only. All specimens and have a high negative predictive value, as compared positive by agar plate were also positive by blood culture with other diagnostic tests. While the results are promis- system. Overall, the blood culture system detected significant- ing, they need to be replicated using large, prospective ly more infections (62 vs. 51, p0.001). Other studies indicate studies of patients presenting with a painful, swollen joint. that blood culture systems might be particularly useful for Such a study base would provide more accurate estimates fastidious organisms such as Kingella and or in of the positive and negative likelihood ratios, since sensi- situations where the patient received antibiotics prior to tivity and specificity calculations can be altered depending arthrocentesis [32, 33]. on SA prevalence. 562 Curr Infect Dis Rep (2012) 14:558–565

Treatment antipseudomonal beta-lactam should be considered. In an era of increasing antimicrobial resistance, including Antibiotics extended-spectrum beta-lactamase-producing Enterobacter- iaceae, individual patients must be evaluated for potential of Management of SA is centered on prompt initiation of resistant pathogens. Risk factors include healthcare expo- appropriate antibiotic therapy—ideally, with drainage of sure, advanced age, , recent surgery, the affected joint(s). Given the low incidence of infection invasive devices, or antibiotic exposure [46]. If any of these and heterogeneity among patient populations, pathogens, risks are present, consideration should be given to use of and management strategies, no reliable guidelines exist , fluoroquinolones, or carbapenems, based for antibiotic choice or duration. A meta-analysis of anti- on the local antibiogram. Lastly, anaerobic infections are biotic selection for bone and joint infection showed no less commonly identified and primarily occur in patients difference in antibiotic efficacy [39]. In the absence of with diabetes mellitus or trauma. high-quality data, antibiotic selection should be guided by With identification and susceptibilities for specific patho- the knowledge of the most likely pathogens and local antibio- gens, antibiotic therapy should be narrowed appropriately. gram and later adjusted on the basis of Gram stain and culture Most antibiotics achieve high concentrations in synovial results (Table 2). fluid [47, 48]. Recently, a retrospective examination of S. aureus and streptococci are most common, and initial and oxacillin for osteoarticular infections due should be active against these pathogens. to MSSA showed no difference in treatment success after MSSA remains more commonly reported than MRSA in SA more than 6 months of follow-up. The authors noted a [12•, 14, 40]. However, in the United States, high rates of higher rate of toxicity with oxacillin and enhanced practi- MRSA, including community-acquired MRSA, should cality of ceftriaxone for outpatient therapy [49]. Similarly, a prompt empiric MRSA coverage until culture results are quasi-randomized trial in childrenshowednodifference known [41]. is most commonly used. In between and first-generation patients with severe vancomycin allergy, daptomycin, line- for MSSA infection [50]. Overall, there are no clear data zolid, tigecycline, or ceftaroline may be considered, al- suggesting superiority of any antibiotic regimen. Treatment though there is less clinical experience with these agents should be selected on the basis of patient- and pathogen- [42–45]. Empiric Gram-negative coverage should be added specific factors. in high-risk patients, including advanced age or risk of In most cases, treatment is started parenterally. If orally gonococcal infection, or in those with indwelling urinary bioavailable drugs are active, clinicians may consider con- catheters, rheumatoid arthritis, underlying immunodeficien- version to oral antibiotics after clinical response is seen. One cies, history of trauma, or history of injection drug use [15, prospective study in children examined parenteral to oral 16•]. Third-generation cephalosporins, such as ceftriaxone, conversion after a mean of 7.4 days and a mean of 18.6 days have commonly been recommended. If Pseudomonas infec- [51]. After 4 weeks of treatment, there was no difference in tion is suspected, a fourth-generation or outcomes. A second pediatric study concluded that conver- sion to oral therapy in children could be safely completed after normalization of C-reactive protein levels [52]. No large Table 2 Empiric antimicrobial regimens trials have been completed comparing parenteral with oral Risk factors Empiric antibiotic choice therapy; however, it is reasonable to convert therapy when an active, highly bioavailable antibiotic option is available and 1. No risk factors Vancomycin or alternate patient adherence is anticipated. anti-MRSA therapy, such as daptomycin or linezolid 2. Elderly, immunocompromised, Vancomycin plus third-generation Joint Drainage recurrent , cephalosporin, such as skin infection or ulceration, ceftriaxone Since joint infection represents a close-space , drain- trauma age of the affected joint(s) is recommended to decrease the 3. Recent healthcare or antibiotic Vancomycin plus carbapenem, exposure, history of resistant fluoroquinolone, or tobramycin inflammatory response and lessen risk of long-term damage, pathogens, or severe illness in based on knowledge of the local particularly to cartilage. Options for drainage include needle patients with risk factors from #2 antibiogram. Consider aspiration, arthroscopy, or , and there have been infectious disease consultation. no direct prospective comparisons of these methods in 4. Risk of disseminated Ceftriaxone adults. Less invasive needle aspiration is desirable if the gonococcal infection joint is easily accessible, the majority of purulent material Note. Antibiotic choices should be modified on the basis of Gram stain can be evacuated, and no negative prognostic factors are and culture results, when available present, including sepsis, neurovascular compromise, long Curr Infect Dis Rep (2012) 14:558–565 563 duration of symptoms, or significant comorbidities [15]. treated with dexamethasone and 62 treated with placebo. They Recent studies have shown success of needle aspiration in found that a 4-day course of treatment lessened children with early septic arthritis, which has tradition- the duration of symptoms in the acute phase and residual joint ally been treated with arthroscopy or arthrotomy due to dysfunction 12 months later [61]. No adverse effects were relative inaccessibility of the joint [53, 54]. Similarly, a reported in either study. Similar studies have not been randomized, controlled trial of needle aspiration versus performed in adults. Overall, the use of in arthrotomy for childhood SA of the shoulder showed equiv- the setting of severe, acute infection must be carefully alent outcomes [55]. Repeat daily joint aspirations are suc- considered due to the potential for immune suppression cessful during the first 5 days of treatment and allow for and decreased antibiotic efficacy, as well as confounding serial monitoring of synovial fluid cell counts and culture to of physical and laboratory features that aid in monitoring ensure treatment response [56]. Alternately, arthroscopy successful joint sterilization. allows for direct visualization of the joint, of necrotic tissue, and intensive lavage to decrease inflamma- Novel Therapies tory mediators and lessen burden of organisms [57]. Deci- sion regarding the optimal route of joint drainage should be Even in the setting of optimal antimicrobial and surgical tailored to the individual patient circumstances and available management of SA, there remains a risk of permanent joint procedural resources. damage and dysfunction. Thus, exploration of novel thera- peutic options is ongoing. In a murine model of S. aureus SA, Treatment Duration tissue destruction continued despite eradication of staphylo- cocci, suggesting an important role for the host response in Few data are available to guide duration and route of anti- promotion of joint damage [62]. Subsequent studies focused microbial therapy. Specifically, no controlled trials have on the host response have shown that TNF-α antagonists, been conducted to determine the optimal length of treatment interleukin-12, and recombinant interleukin-10 could be used in children or adults. Small case series and expert opinion adjunctively with antibiotics for their anti-inflammatory have led to traditional recommendations for 2–4 weeks of effects [3•, 63–66]. The addition of bisphosphonates to anti- treatment. In one series of 130 cases of SA in children, 63 biotics has also shown benefit in animal models. Verdrengh patients were treated for 10 days with clindamycin or a first- and colleagues showed that mice treated with zoledronic acid generation cephalosporin, and 67 patients were treated for and antibiotics with or without corticosteroids lost less trabec- 30 days. There was no difference in rates or recrudescence ular bone density, as compared with infected controls. Use of or long-term sequelae 12 months later [58]. Common recom- bisphosphonates to decrease osteoclastic activity may reduce mendations suggest the following courses of therapy: 2 weeks the risk of skeletal destruction [67]. These potential therapeu- for streptococci or Gram-negative cocci, 3 weeks for staphy- tic targets are experimental and have not been examined in lococci, and 4 weeks for pneumococci and Gram-negative humans. Thus, additional research is necessary regarding their bacilli [31]. However, this clinical decision should be individ- potential clinical benefit. ualized on the basis of the patient’s comorbidities, identified pathogen, severity of illness, presence of associated osteomy- elitis, and response to therapy. Conclusion

Corticosteroids In an aging and increasingly immunocompromised popula- tion, clinicians need to be aware of the urgency involved in The use of corticosteroids for suppression of excessive identifying and treating native joint SA. This remains a chal- inflammation has been considered, but data showing effica- lenging diagnosis due to the absence of specific physical cy and safety are scarce. In a murine model of hematoge- examination findings and limited diagnostic modalities. How- nously acquired S. aureus SA, treatment with intraperitoneal ever, with further investigation into synovial cell counts in corticosteroids reduced the severity of arthritic symptoms larger patient populations and enhancement of culture techni- and mortality [59]. Two studies have evaluated the use of ques, there is potential for improved diagnosis. Similarly, PCR dexamethasone in children with SA. In a series of 49 children, provides a new method for pathogen identification and sub- Harel et al. randomized patients to receive dexamethasone or sequent targeted antibiotic therapy. Empiric antibiotic regi- placebo [60]. As compared with placebo, dexamethasone- mens in the United States should include treatment of treated patients experienced shorter duration of fever, local MRSA, and in certain high-risk group, Gram-negative bacte- inflammatory signs, and pain. Additionally, use of dexameth- rial coverage. Additional research into the optimal antibiotic asone was associated with shorter duration of treatment and regimens is needed to enhance patient outcomes and further hospitalization. Similarly, Odio et al. compared 61 children efforts for antimicrobial stewardship. 564 Curr Infect Dis Rep (2012) 14:558–565

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