Prosthetic joint infection of the hip and knee due to Mycobacterium species: A systematic review

lNTRODUCTlON

The incidence of prosthetic joint infection (PJI) has increased with an increase in the number of patients undergoing total joint arthroplasty, particularly hip and knee arthroplasties[1]. The cumulative incidence of PJI after total hip arthroplasty (THA) and total knee arthroplasty remains unclear; however,it is believed to range between 2.05% and 2.18%. The majority of PJI cases are caused by gram-positive cocci such asand coagulase-negative(60%); however, sometimes they can also be caused by gram-negative bacteria, such asor[2,3].infections account for approximately 2% of all PJI cases[4].() is an infrequent cause of PJI, accounting for only 7 cases (0.3%) as reported during a 22-year period at one center[5]. However, in tuberculosis-endemic countries, patients undergoing joint arthroplasty with previous tuberculous septic arthritis are at an increased risk of developingcomplex PJI[1]. Some other(rapidly growing) are reported to grow rapidly, and they spread in various environments worldwide[4].

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Appropriate management is mandatory to prevent complications that arise from PJI. Successful management of PJI is achieved by a combination of surgical intervention and appropriate medical therapeutic strategies to eradicate infection, reduce pain, restore function, and prevent prolonged antimicrobial therapy in patients[1,2,6]. The diagnosis of mycobacterial infections is often delayed due to the low index of suspicion, clinical and laboratory presentation that mimics bacterial infections, and low yield of smears and culture for acid-fast bacilli. Moreover, mycobacterial infections are often known to occur together with other bacteria, such as coinfection or superinfection[2,6]. Delayed diagnosis and prevention of PJI can lead to prolonged illness with various dangerous manifestations that can threaten the patient’s life. Althoughare not among the common causative agents of PJI, it is important to recognize and treat them differently from non-mycobacterial infections. The aim of this study was to identify and evaluate the profile of PJI cases due to mycobacterial infection in the hip and knee as published over the past 30 years.

Search strategy

A literature search was performed using MeSH terms on PubMed from January 1, 1990, to May 30, 2021.The following two search scenarios were used accordingly: “Prosthesis joint infection AND Mycobacterium” and “Arthroplasty infection AND Mycobacterium”. The articles were screened based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.

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Inclusion and exclusion criteria

The following inclusion criteria were used in our systematic review: (1) Clinical studies; (2) All levels of evidence; and (3) PJI of the hip or knee due to any(). Studies were excluded if they met any of the following criteria: (1) Non-English articles; (2) PJI not involving the hip or knee joint; (3) Primaryhip/knee osteoarticular infection prior to arthroplasty; (4)Articles published in abstract form only; (5) Review articles; and (6) Technique articles.

Data collection/extraction

More than 150have been officially recognized until now, in literature which consist of tuberculous mycobacteria and NTM[56]. One of the purposes of this systematic review was to evaluate the variousthat can cause hip/knee PJI, and at least 17were identified accordingly. They comprised ofand 16 NTM. The NTM was further divided into rapidly growing and slowly growing mycobacteria[56]. Several studies have reported rapidly growing NTM as the cause of early hip/knee PJI[4,17,18,28]. Early PJI (≤ 3 mo) was noted in 36% of the NTM cases in this review, which was higher than that in tuberculous PJI cases (11%). The rapidly growing NTM hence needs to be considered as a differential diagnosis in cases of early hip/knee PJI. The diagnosis ofPJI is sometimes delayed, leading to delays in appropriate management[6,8]. Several treatment options were noted in this review. Removal of the prosthesis was the most commonly performed procedure, which was required in ＞ 75% of cases. Additionally, a greater number of NTM PJI cases required removal of the prosthesis compared to the tuberculous PJI cases (88.9%58.1%). There were no data regarding specific procedures, such as revision surgery, resection arthroplasty, or arthrodesis after the prosthesis removal procedure due to incomplete data in every published article.Another interesting finding was that conservative treatment with only antimicrobial therapy successfully controlled tuberculous hip/knee PJI in approximately 23% of the cases. This indicates that early recognition of sensitive antimicrobial agents is highly important in treatingPJI.However, the isolation ofwith standard culture procedures may be sometimes difficult and more advanced techniques with gene sequencing are hence needed to isolate the[19]. This could be a hindrance, especially in developing countries. Based on the pooled case analyses reported from the studies included in this systematic review, the outcome of the treatment ofPJI reportedly had an infection control rate of approximately 86%. Among the mycobacterial PJI cases, the infection control rate of nontuberculous PJI was comparable to that of tuberculous PJI (91.7%81.4%,= 0.092). This was comparable to that of PJI hip/knee associated with non-mycobacterial pathogens or even a negative-culture PJI that showed an infection control rate of 70%-90%[3,57].PJI has also been correlated with culture-negative PJI. A study by Palan[58] reported that fungi and mycobacteria are responsible for over 85% of negative-culture PJI. Arthroplasty surgeons need to consideras the causal pathogen of PJI when negative culture results are obtained in clinical practice. Further diagnosis using histopathology or polymerase chain reaction assay is needed accordingly.

RESULTS

Of the 51 included studies, 40 (80.3%) were case reports and 11 (19.6%) studies were of the retrospective series type. There were studies from America (27/51, 52.9%), Europe (12/51, 23.5%), and Asia-Pacific(12/51, 23.5%) included in the analysis. In total, 117hip/knee PJI cases were reported across 51 studies. There were 46.15% (54/117) cases of knee PJI and 53.85% (63/117) of hip PJI, and the age range of the patients was 17-101 years. In total, 17 types ofrecorded in this review were responsible for PJI in 115 hip/knee PJI cases, whereas in 2 cases there was no mention of any specific.was detected in 50/115 (43.3%) of the cases. The NTM included(26/115, 22.6%),(10/115, 8.6%),(8/115, 6.9%), and(8/115,6.9%). Other strains with a smaller number of cases were also isolated as the causes of hip/knee PJI(Figure 2). Mixed infections in mycobacterial PJI cases were noted in 8 cases caused byand(all NTM) in 1 case and byandin another. The other six cases showed co infection with. The majority of the cases (82/114, 71.9%) showed an onset of infection ＞ 3 mo after the index surgery, whereas 24.6% (28/114) of patients showed disease onset in ≤ 3 mo. Incidental intraoperative PJI diagnosis was reported in 4 cases (3.5%) (Figure 3A), and it was not specified in 9 cases. Removal of the prosthesis (with or without revision) was needed in 77.8% (84/108)of cases to treat the infection (Figure 3B). While debridement was needed in 11/108 (10.2%) cases,antimicrobial therapy was needed in 12/108 (11.1%), and amputation was performed in 1 case. The overall infection rate was controlled in 88/102 (86.3%)PJI cases. Persistent infection occurred in 10/102 (9.8%) patients, and 4/102 (3.9%) patients died due to the infection (Figure 4).Comparative analysis showed no difference in the rate of hip or knee involvement in PJI withor NTM (＞ 0.05). BothandPJI cases predominantly showed disease onset of ＞ 3 mo (79.1% and 63.3%, respectively). However,PJI cases showed a higher rate of early onset (＜ 3 mo) of disease than those cases with tuberculous PJI (36.7%11.6%).Removal of the prosthesis was needed in more cases of nontuberculous PJI than in cases of tuberculous PJI (88.9%58.1%). The infection control rates were comparable between the tuberculous and nontuberculous PJI cases (81.4% and 91.7%, respectively) (Table 2).

DlSCUSSlON

Three authors (Santoso A, Phatama KY, and Rhatomy S) independently screened the titles and abstracts of the included studies. The first search with the terms “Prosthetic joint infection AND Mycobacterium”revealed 54 records. Of these, 6 records were excluded for not being in English, 5 for presenting primary osteoarticular hip/knee infection, 2 for presenting shoulder/elbow PJI, 1 for presenting wound infection after THA without involvement of the joint, and 3 for unavailability of the full-text articles. The remaining 37 records were included in the further analysis. The second search method was performed with the words “Arthroplasty infection AND Mycobacterium”, which revealed 56 records. Of these, 33 records were excluded for duplicating previous search results, 4 for presenting primary hip/knee osteoarticular infection, 1 for presenting shoulder PJI, 1 for being a non-English article, 2 for being review articles, and 1 for unavailability of the full-text article. Thus, 14 records were finally included from the second search in the analysis. Considering the 37 records from the first search and 14 from the second search, a total of 51 records were included in the final analysis (Figure 1). The analysis included type of study, demographics, number of patients, hip or knee PJI cases,strain,treatment, and outcomes of the mycobacterial PJI cases (Table 1). Furthermore, we performed a descriptive comparison between PJI caused by(= 43) and(NTM) (= 63). This comparative evaluation excluded all cases of mixed infections ofand NTM (= 1), NTM and() (= 2), andand(= 6). Two cases with no data 5 regarding the specific species ofwere also excluded at this stage (Table 2). Comparative analysis of categorical data was performed using the chisquare test.

We found at least 17 species ofcould be responsible for hip and knee PJI.

CONCLUSlON

At least 17can be responsible for PJI of the hip and knee. Althoughis the most common causal pathogen, NTM should be considered as an emerging cause of hip/knee PJI.

ARTlCLE HlGHLlGHTS

Research background

To do compilation data of Mycobacterium species (Mycobacterium sp) which may cause hip and knee PJI.

Research motivation

There were many species of Mycobacterium that may be associated as a causal pathogens for prosthetic joint infection (PJI) of the hip and knee. However, no available literature which provides compilation data regarding this issue.

Research objectives

This study aimed to evaluate PJI associated with Mycobacterium sp.

Research methods

We highly thank Denny Adriansyah, MD for his assistance in data collection and analysis.

Research results

All of the author have none to disclose.

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Research conclusions

This study had a few limitations. First, the systematic review only included studies indexed in PubMed; therefore, some other studies may have been missed in this review. However, the wider search period (30 years) of this systematic review ensured the inclusion of several important studies from literature. Second, the studies included in this systematic review were mostly retrospective case reports or case series, which had their own limitations. It is difficult to obtain a higher level of evidence from relatively rare cases, such as those ofPJI. Third, some bias of treatment and outcome evaluation may have occurred, as every author may have used a different standard. This study also could not suggest any advisable best treatment forPJI due to the lack of available data for evaluation. Despite these limitations, we believe that this systematic review could provide some insights into the profile ofhip/knee PJI, including its treatment options and outcomes.

Research perspectives

This study may open the knowledge of various species ofthat can be associated with hip and knee PJI.

ACKNOWLEDGEMENTS

Systematic review of PubMed article.

FOOTNOTES

Santoso A, Phatama KY, and Rhatomy S contributed to the data collection and analysis;Santoso A and Phatama KY wrote the paper; Budhiparama NC contributed to the study design, analysis and finalization.

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Among reviewed 51 articles. We found several species of Mycobacterium may be associated with hip and knee PJI.

This study has been presented following the PRISMA 2019 Checklist.

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Asep Santoso 0000-0002-8170-4055; Krisna Yuarno Phatama 0000-0003-1050-7561; Sholahuddin Rhatomy 0000-0002-5512-6706; Nicolaas Cyrillus Budhiparama 0000-0002-0801-7400.

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