Management of septic arthritis of the hip joint in adults. A systematic review of the literature

Background The septic arthritis of the hip is a complex condition characterized by a variety of clinical presentations, a challenging diagnosis and different surgical treatment options, including arthroscopy, resection arthroplasty and one and two-stage total hip replacement. Each technique reports variable results in terms of infection eradication rate. The aim of this systematic review is to compare the most relevant studies available in current literature and to assess if a better treatment outcome can be predicted based on the microbiology, history, and type of infection (active vs quiescent) of each case. Methods A systematic review of the literature was performed in accordance with the PRISMA guidelines, including the studies dealing with the treatment of hip septic arthritis in adult patients. Electronic databases, namely the MEDLINE, Scopus, and Web of Science, were reviewed using a combination of following keywords “septic arthritis” AND “hip joint” OR “hip” AND “adult”. Results The total number of patients included in this review was 1236 (45% of which females), for 1238 hips. The most common pathogen isolated was Staphylococcus aureus in its Methicillin-sensitive variant ranging from 2 to 37% of cases. Negative cultures were the second most common finding. It was also differentiated the type of infection of the hip, 809 and 417 patients with active and quiescent hip infection, respectively, were analyzed. Eradication rates for two-stage revision arthroplasty ranged between 85 and 100%, for one-stage approach between 94 and 100%, while for arthroscopic debridement/lavage between 89 and 100%. Conclusion Staphylococcus aureus is the most common microorganism isolated followed by culture negative infections. Arthroscopic, one and two stage procedures can be effective in the treatment of hip septic arthritis when the indication is consistent with the type of infection retrieved. Level of evidence IV, therapeutic study.

Due to the possible clinical presentations, which may vary based on age [4], type of infection and etiology, the diagnostic workup and definitive treatment require a multidisciplinary approach.A timely diagnosis is essential in order to avoid a delayed treatment which could result in quality life-altering consequences for the patient [5].Furthermore, several algorithms tried to standardize the diagnostic procedures and treatment of septic arthritis, but no consensus has been reached so far, probably due to the small number of patients included in the studies available.
Various surgical treatment options are currently available for the orthopedic surgeon facing a SA including arthroscopic lavage/debridement, resection arthroplasty (arthrotomy) and Total Hip replacement (THR) in one or two stages [6,7].The Second International Consensus Meeting (ICM) on orthopedic infections in 2018 tried to standardize the treatment of the patient with SA differentiating between active and quiescent local infective process of the hip or knee [8].Patients with quiescent infection often reported a distant history of infections and the clinical and laboratory investigations including serum, synovial aspirate and imaging studies demonstrated no symptoms and signs of active infections.Recently, a systematic review by D' Angelo et al. found that arthroscopy, single open or two-stage THA are effective in treating bacterial septic arthritis of the native hip [9].Since then, some additional studies have assessed the treatment outcomes of septic arthritis of native adult hip.Therefore, we carried out an updated systematic literature review to further address the success rate and outcome of patients affected by hip SA surgically treated.

Search strategy and criteria
This systematic review was conducted according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA ) [10].Electronic databases, namely the MEDLINE, Scopus, and Web of Science, were reviewed for studies investigating the treatment of hip septic arthritis in adult patients.A combination of following keywords was used for article search: "Septic arthritis" AND "hip joint" OR "hip" AND "adult".The inclusion criteria were not limited to English language literature and specific publication dates.Reference lists of selected articles were searched for any additional articles that were not identified in the database search.Longitudinal studies (retrospective and prospective) evaluating patients affected by hip septic arthritis surgically treated were included.The exclusion criteria included: case reports, expert opinions, prior systematic reviews, letters to the editor and studies that included different joints involved in which hip data could not be extrapolated.

Study assessment and data extraction
Initially, the titles and abstracts of the studies were screened by two pairs of independent reviewers (RdG, EM).Full text was obtained for all the abstracts that appeared to meet the inclusion criteria or those with any uncertainty.Then, each study was assessed based on the inclusion criteria by two independent reviewers and any disagreement regarding inclusion of any particular study was resolved by evaluation of the article by the senior author (GB).
The flow diagram of our search strategy is presented in Fig. 1.A total of 1227 potentially relevant studies were found through computer search and manual screening of reference lists; 288 were duplicates and were removed.After screening the titles and abstracts, 836 studies were excluded, and 103 full texts were evaluated.69 studies were excluded after a detailed assessment and the remaining 34 articles were included in our systematic review [1,[3][4][5].
Relevant data were extracted from each included study.Data describing participants demographics, microbiology, treatment options and outcomes were recorded.

Patient analyzed
Table 1 summarizes the characteristic of the included studies.A total of 1236 patients (1238 hips) affected by septic arthritis were evaluated.Based on reported data, hip infection occurs in patients with a mean age ranging from 24 to 65 years.Of 1116 patients, 45% were female [1, 4, 11, 13, 16-22, 25-33, 35, 36, 38-41].All studies included in our systematic review clearly described the type of infection distinguishing the septic process in active or quiescent as established during the second International Consensus Meeting in Philadelphia [8].Active infection is defined as the presence of clinical and laboratory findings of local infection while a quiescent infection refers to an history of septic arthritis with no signs of active infection.We included 809 and 417 patients with active and quiescent hip infection, respectively.The mean follow-up was reported in all studies included ranging from 3.3 months [25] to 182.4 months [4].

Etiology and pathogenesis
All but six [17,20,22,23,37,40] of the included studies clearly stated the pathogens responsible for the hip SA (Table 2).In each of these studies the species Staphylococcus aureus was the most common finding, with the exception of the study by Li et al. [28], in which all the presented hip SA were sustained by Mycobacterium tuberculosis, and 4 studies in which the majority of patients had negative culture infections.Methicillin-sensitive Staphylococcus aureus (MSSA) was responsible for SA in a percentage of patients that varied from 2 to 37% [3,11,14,18,24,30,32,35,36,39,41], while 3 found an higher isolation rate for Methicillin Resistant S. aureus (MRSA) [13,15,31].
Furthermore, Russo et al. [35] described that the 76% of septic arthritis were primary infections with a diagnosis based on one or a combination of clinical signs of infection, elevated serum C-reactive protein (CRP) and erythrocyte sedimentation rate ESR values, radiographic findings of bone resorption and/or loss of articular space, intra-operative purulence, and positive intra-operative and/or synovial fluid microbiology.

Treatment options
Three main surgical options recommended for the treatment of septic arthritis such as arthroscopic debridement/lavage and one-stage or two-stage (either after resection arthroplasty or an antibiotic-loaded spacer implantation) total arthroplasties (Table 3) were described.Among the studies included in our systematic review 16 [1, 11-16, 18, 25, 26, 28, 32, 35, 37, 38, 41]   reported a two-stage surgical treatment of the hip's SA.In twelve papers [11, 13-16, 18, 25, 26, 28, 35, 37, 41] a two stage procedure was the only treatment evaluated, while in 3 studies [1,12,32] two-stage and one-stage procedures were considered.One stage procedure was performed in 446 adult patients affected by septic arthritis of native hip [1,4,20,23,29,33,40]. Proximal femur arthrotomies weren't practiced as the only procedure in any of the articles included in this review but were part of one or two stage procedure valued in 6 studies [1,3,13,17,22,31] and utilized as a salvage operation by Anagnostakos et al. [11] and Park et al. [33] whenever the two or one-stage procedure failed.Arthroscopic and open debridement were the treatment option in 79 and 7 patients, respectively.As for antibiotic therapy protocols, 7 studies [20,22,23,29,32,33,40] didn't mention what therapy had been conducted during the treatment of SA and for how long.
Successful treatment of SA, defined as infection eradication rate after antibiotic discontinuation, was reported in 32 papers included in the systematic review ranging from 62% [5] to 100% of patients.Two-stage procedures have reported a high eradication rate following the second-step surgery, ranging from 85% [12] to 100% [11,14,15,28,32,35,37].
The management of failed patients that experienced a persistent infection varied among the studies.Only 9 of the 36 articles included in this review described their management of failed cases (Table 3).
Timing from diagnosis of septic arthritis to surgical procedure varied across the valued papers: 5 of 34 papers mentioned this parameter.Anagnostakos et al. [11] diagnosed infection between 4 weeks and 6 months prior to surgery, while Romanò et al. [41] between 6 and 9 months.Yamamoto et al. [39] and Fukushima et al. [19]

Discussion
Septic Arthritis of the hip is a disease with a relative low incidence [2] but causes pain and disability to the affected patients with a mortality rate estimated to hover around 10%.Methicillin sensitive Staphylococcus aureus appears to be the most common causative agent for septic arthritis of the hip.The culture negative infections occur in a percentage that varies from 16.7 to 78.4% of the cases [1,3,5,11,14,15,18,19,[24][25][26][27]30,32,35,36,38].The treatment of hip infection in adult patients is influenced by several factors, but the choice of the best option depends on the type of infection (active or quiescent).Various surgical treatment options are currently available for the orthopedic surgeon who faces a SA such as arthroscopic lavage/debridement, resection arthroplasty (arthrotomy) and Total Hip Replacement (THR) in one or two stages.
The chosen treatment wasn't influenced by the age of the patients in any of the reviewed articles, but, noticeably, Nusem et al. [30] treated exclusively with arthroscopy the youngest cohort of patients among all papers.
Arthroscopy is usually effective to remove infective materials and to debride necrotic tissues.Although Flores-Robles et al. [3] highlighted that the arthroscopic debridement of the hip SA reported a lower recurrence of infection than conservative approach, more than one procedure is often mandatory to resolve the infection process [27].
The resection arthroplasty as described by Girdlestone in 1943 may be effective on eradicating the infection, but the sequelae include chronic limp, length discrepancy, and only partial pain relief, even though the procedure itself has been vastly modified over the years [35].One and two-stage THR, whether the first step was constituted by a resection arthroplasty or the implantation of an antibiotic-loaded hip spacer, have proven to be very effective on eradicating infection and have excellent long term functional outcomes [6,7,14,26], but require consistent technical skill to face the deformities caused by the SA (deformation of the acetabulum, insufficient bone stock in the superolateral acetabulum leading to insufficient coverage of the cup, and abnormal positioning   of the hip contributing to accelerated aseptic loosening, etc.) [40] and the resources to support potential longer hospital stays and higher costs for implants [1].Chen et al. [13] reported on a 28-hips population treated with a Girdlestone arthrotomy followed by a THR, with an average follow up of 77 months and a rate of eradication for infection of 86%, suggesting that implanting an antibiotic-loaded spacer may help to improve the microbiological efficacy of the treatment.In the study by Choe et al. [15] the two-stage procedure was applied to 27 patients suffering from both SA and PJI, with similar functional outcomes and a full 100% of free-from-infection (defined as serum CRP decreased to less than 1 mg/dl or for maximum of 3 months) patients at a 33 and 38-months period, respectively.Li et al. [28] reported a 100% eradication rate from tubercular SA treating patients with either spacer implantation or extensive debridement alone during a first surgical step, preceded by 2 weeks of antitubercular chemotherapy and followed by for at least 3 months of the same pharmacological protocol, plus 9 months after the THA for a total of 12 months.One stage treatment showed equal if not higher infection eradication rates (85% vs 100% according to Bauer et al. [12] on 22 cases with 60 months follow-up) with correct diagnostic work-up to treatment and timing.
Recently, the second international consensus meeting on peri-prosthetic joint infection tried to standardize the treatment of the patient affected by septic arthritis differentiating between active and quiescent local infective process of the hip or knee.Patients affected by quiescent SA present a history of infection with no clinical, laboratory and radiological signs of local active infection.
One-stage arthroplasty is recommended for quiescent infections instead of two-stage arthroplasty that is indicated in those patients affected by active infections at the time of arthroplasty [8].The success rate seems to be quite similar between one and two stage when performed in patients affected by quiescent and active infection, respectively.This study has a few drawbacks.First, this systematic review was performed on level II or level IV small case series.Moreover, the lack of standardization between papers regarding the joint damage, host, pathogen and diverse techniques may have contributed to heterogeneity between studies.This limitation prevented us to compare techniques especially for the infection eradication rate.

Conclusion
The evidence emerged from this review suggests that Staphylococcus aureus is the most common microorganism isolated followed by culture negative infections.The specific pathogen responsible for a given infection, including negative cultures, wasn't a criteria for the selection of the surgical option, but rather it modified the antibiotic protocol followed by each patient.Arthroscopic, one and two stage procedures can be effective in the treatment of hip septic arthritis taking in consideration the type of infection.However, further perspective studies would be needed to establish an algorithm of treatment options.

Table 1
Characteristics of the studies included in the systematic review

Table 1
(continued) N.A.Not Available

Table 2
Microbiological findings and the cause of hip septic arthritis

Table 3
Treatment options and clinical outcomes of Septic Arthritis of Hip

First author, year, Nation No Hips Treatment One stage vs two stage vs arthroscopy Duration antibiotic treatment Outcome (infection eradication rate) Treatment failure
N.A.Not Available