Introduction
Periprosthetic joint infection (PJI) is a devastating complication following total joint arthroplasty (TJA) and accounts for the majority of postoperative revisions [
1,
2]. Meanwhile, it brings a huge economic burden to the healthcare system each year [
3‐
5]. Therefore, the prevention of PJI cannot be overemphasized. Recently, more and more surgeons have emphasized the importance of improving modifiable risk factors preoperatively [
6‐
9]. The nasal
Staphylococcus aureus colonization is generally considered to be one of the modifiable risk factors [
6].
Some studies showed that the routine implementation of nasal screening and selective decolonization could significantly mitigate the risk of surgical site infection (SSI) following TJA [
10‐
13]. However, it is still controversial, because several studies suggested the opposite conclusion [
14,
15].
Therefore, the purpose of this systematic review and meta-analysis was to quantitatively evaluate (1) was there any association between the nasal carrying of S. aureus and the high rate of SSI or PJI after primary elective total hip and total knee arthroplasty (THA and TKA), (2) could preoperative nasal S. aureus screening and decolonization reduce the rate of SSI and PJI, and (3) was the routine S. aureus screening necessary before TJA.
Methods
This study was conducted strictly according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement [
16]. Before the start of literature searches, the research protocol was determined by all coauthors.
Search strategy
Following the PICOS methodology, two authors (Xingyang Zhu and Xiaobo Sun) developed the search strategies with the assistance of an experienced librarian. The last database search was performed on October 18, 2019 with comprehensive strategies, including both Medical Subject Headings and keywords, for the following electronic databases: MEDLINE (PubMed), EMBASE (Elsevier platform), and COCHRANE CENTRAL (through the Cochrane-Library). When searching, we had no restrictions on the language and publication date of the articles to maximize the sensitivity. Additionally, reference lists of relevant articles were also screened to identify additional studies. See Appendix
1 for the full and detailed search strategy
.
Inclusion and exclusion criteria
Two independent authors assessed the titles or abstracts or full text of the final search results. In case of any controversy that arose between the two reviewers (Xingyang Zhu and Xiaobo Sun) regarding eligibility, an agreement could be reached through discussion. If no consensus was achieved, the final decision was made by the third author (Yirong Zeng).
The inclusion criteria were listed as follows: (1) all surgical procedures were primary THA or TKA; (2) data detailing SSI rate in patients with or without preoperative S. aureus screening and decolonization after primary THA or TKA were complete; (3) sufficient data were provided for calculating pooled odds ratios (OR) with a 95% confidence interval (CI); (4) specific information on the measures of S. aureus screening and decolonization as well as the antibiotic application perioperatively was available.
The following exclusion criteria were used: (1) those studies that the data of interest were incomplete; (2)patients were treated with emergency joint replacements (e.g., hip arthroplasty for femoral neck fracture) or revision surgeries; (3) research contained other orthopedic surgeries; (4) full manuscript was not available; (5) reduplicative studies of the same patients in different periods; (6) reviews, commentaries, editorials, and letters were excluded; (7) languages were not accessible to authors.
Study quality assessment
The methodological study quality was assessed using the Newcastle-Ottawa Scale (NOS), a validated tool suitable for cohort and case-control study [
17]. Two reviewers assessed the studies independently, resolved divergences through discussions or reached consensus with the third author.
Pertinent data were extracted by two reviewers independently from all eligible studies using a standardized data collection form, including the following variables: author, year of publication, country, type of study, number of TJR, type of arthroplasty (THA, TKA, or both), the methods of S. aureus screening and decolonization, application of perioperative antibiotics, definition of PJI, and any wound complications, number of SSI (PJI and superficial infection), and infection rates of S. aureus and other bacteria. For research lacking the results we needed, we had contacted the author(s) via email for more information.
The primary outcome of this research was SSI. However, different studies followed various definitions of SSI and PJI. Therefore, similar to Bedard et al. [
7], “any wound complications” and “PJI” were used to pool end points of reported infection. “Any wound complications” was defined as any postoperative wound complications reported in the included studies, while PJI was defined as any deep infection involving prosthesis. The secondary outcome was the infection rate of
S.
aureus and other bacteria between the two groups.
Statistical analysis
The OR and associated 95% CI were used to perform estimates for dichotomous variables, while the mean ± standard deviation was used for continuous variables. Only research that contained both OR and CI could be included in the analysis. P values < 0.05 were considered to be statistical significance.
The I2 and p value were used to evaluate the statistical heterogeneity across studies. If the heterogeneity test indicated the p values > .1 or I2 < 50%, the fixed effect model would be applied. On the contrary, if the heterogeneity test expressed the p values ≤ .1 or I2 ≥ 50%, the random effect model would be used. If necessary, a sensitivity analysis was conducted to assess the stability of the results. If data were available, subgroup analysis was also conducted to get more specific conclusions. In addition, forest plots were used to depict the results of each study and evaluate pooled estimates respectively, and the funnel plots were used to evaluate publication bias. All statistical analyses were performed through Review Manager (version 5.3.5 for Windows; The Cochrane Collaboration, The Nordic Cochrane Center, Copenhagen, 2014).
Discussion
This systematic review and meta-analysis included nine independent studies that analyzed 36041 cases of arthroplasty and directly assessed the effectiveness of S. aureus decolonization and nondecolonization in SSI following primary THA and TKA procedures. The pooled analyses indicated that S. aureus screening and decolonization reduced the SSI (both PJI and superficial infection). And further research suggested a decrease in SSI caused by S. aureus, while there was no difference in SSI caused by other bacteria between the two groups.
The nasal cavity is one of the most common sites for
S.
aureus colonization. One study revealed that the nasal colonization rate of
S.
aureus was 22.2% and that of MRSA was 0.8% [
15]. Another study also showed that colonization rate of MSSA was 22.6% and that of MSRA was 4.4% [
40]. It is generally believed that
S.
aureus in the nasal cavity is one of the potential sources of bacterial seeding for SSI. The methods of
S.
aureus screening mainly include bacterial culture and real-time polymerase chain reaction (RT-PCR).
Currently, the common method for
S.
aureus decolonization is that topical application of mupirocin twice daily to both nares accompany with or without chlorhexidine showers or skin wipes daily for 5 days prior to the TJA [
41]. However, several studies implemented an extensive decolonization program, regardless of whether
S.
aureus was positive or not [
4,
12,
37], which may be considered an abuse of antibiotics and may lead to an increased risk of bacterial resistance. Therefore, it may be more reasonable to perform selective decolonization programs for only screened positive patients.
Conventional application of this regimen to patients with positive
S.
aureus preoperative has shown good short-term results in improving decolonization rates [
4]. However, its long-term efficacy is uncertain. Many studies showed that a significant number of patients would remain positive for
S.
aureus after surgery [
42,
43]. For example, a study revealed that 33% (19 of 58) of patients still performed positive for
S.
aureus colonization at 3–30 months after surgery despite preoperative decolonization [
44]. Another recent study also showed that the screening and decolonization regimen did significantly reduce the number of nasal carriage of MRSA, but the study also showed that about 20% of patients might remain colonized by MRSA despite a decolonization protocol in patients undergoing Elective TJA [
28]. This means that a decolonization treatment could not guarantee that patients will keep decolonized in the future, which requires further research, because it is still unclear whether the risk of late infection in this population is higher [
44].
So far, whether the
S.
aureus decolonization program could reduce the SSI in patients undergoing primary TJA is still controversial. Numerous studies showed that SSI could be decreased by an institutional nasal screening and decolonization protocol for patients before elective TJA regardless of carriers of either MSSA or MRSA [
38,
40]. For instance, Sporer et al. [
38] demonstrated a 69% reduction in the prevalence of SSI after the use of screening and decolonization program. Similar to this study, Kim et al. [
40] also reported a 59% reduction in SSI after implementing a similar screening protocol, and they found that MRSA carriers had a higher rate of SSI than that of non-carriers (0.97% vs. 0.19%). Therefore, nasal carriage of
S.
aureus has been considered as an independent risk factor for SSI and PJI. Conversely, several recent studies demonstrated that nasal decolonization protocol prior to elective TJA could not decrease the incidence of SSI [
14,
15,
28]. After comparing the infection rates of colonized and noncolonized patients, Ramos et al. [
14] discovered that the risk of infection in decolonized patients could not be decreased to the baseline level of nondecolonized patients. A prospective randomized trial also demonstrated that there was no significant difference between treated and untreated carriers and that most of
S.
aureus PJI occurred in non-carriers, so the authors believed that there was no clear benefit in screening and/or decolonizing carriers before TJA [
15].
Based on the included studies, our pooled data showed that
S.
aureus screening and decolonization dramatically reduced the incidence of SSI. However, it should be noted that in these studies, patients screened positive for MRSA also received vancomycin as a standard perioperative antibiotic prophylaxis, so it did not rule out that the decrease of infection rate might be caused by the use of vancomycin, which needs to be further studied. Additionally, Jeans et al. [
36] reported that MSSA screening and decolonization might be more effective in decreasing overall infection rate in hips than in knees. Unfortunately, due to insufficient data in this area, we are unable to conduct relevant analysis.
To the best of our knowledge, this is the most comprehensive meta-analysis examining the association of
S. aureus screening and decolonization with SSI after TKA and THA. We are aware of previous meta-analyses on this topic [
30,
45,
46]. Studies performed by Levy et al. [
45] and Chen et al. [
46] contained other orthopedic surgeries, which would lead to a mass of confounding factors. In another very recent paper performed by Sadigursky et al. [
30], only four studies were included in the analysis. Compared with these studies, we included some new clinical studies up to 2019. Moreover, we strictly assessed the quality of all selected studies and followed the PRISMA statement in this study.
Although we have designed and implemented the research as perfectly as possible, our meta-analysis still inevitably has several inherent limitations. First, as all systematic reviews, some studies would be ignored because of search strategies. In order to overcome this problem as much as possible, we consulted professional librarians and optimized search strategies continuously during the search process. Second, most of the included studies were retrospective rather than prospective, and follow-up duration of some selected studies was short (about 30–90 days), which might prevent late PJI and SSI from being observed. Third, the diagnostic criteria of PJI and SSI in different studies were not uniform, and preoperative treatment with vancomycin might affect the outcomes for patients screened positive for MRSA. Finally, the data analysis in this paper were performed at the research level rather than at the patient level; therefore, we could not take each patient's physical status, age, gender, diagnoses, body mass index, American society of anesthesiologist (ASA), duration of surgery, nutritional status, and follow-up times into account, all of which might affect the results. Given the above shortcomings, more prospective and long-term follow-up studies are still needed to better understand the impact of the S. aureus screening and decolonization on the incidence of SSI and PJI after TJA.
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