In this study, no risk factors for MRSA were identified and the risk factor for S. aureus carriage was female sex only. As for S. aureus carrier status, specificity of female sex as a risk factor was 0.129. Because of low specificity, implementing the TS strategy considering this risk factor would require screening a considerable number of patients—amounting to 88.5% of all patients—with 4 of 29 (13.8%) MRSA-positive cases and 34 of 445 (7.6%) S. aureus-positive cases being overlooked. Thus, this parameter is not useful and no suitable risk factor for the TS strategy was identified.
Previous studies have attempted to clarify various risk factors, including male sex, white race, obesity, asthma [12], diabetes [13], and renal disease [14] for both MSSA and MRSA colonization, but opinions remain divided. While smoking was described as a risk factor in one study [15], it was found to have no relationship with S. aureus colonization in other studies [1,12]. De Wouters et al. reported that although Belgian guidelines recommend TS for MRSA carriage on admission for high-risk populations only (age > 80 years; inpatient admission in the previous 6 months; past history of MRSA colonization; living in a nursing or residential home; exposure to invasive devices; chronic wounds or skin lesions; working in health care; and being in contact with farm animals), there was no correlation between identified MRSA carriers and these risk factors [16]. No risk factors for MRSA were identified in this study. Moreover, when female sex was applied as a risk factor for TS, the average cost of US vs TS per person to decolonize S. aureus-positive cases was 1201.6 vs 1160.4 yen; thus, TS could reduce costs by 41.2 yen (3.6%) compared with US. As such, no useful predictive factors that enable the successful implementation of TS were identified and the strategy was also not that cost-effective.
The UD strategy is advocated in clinical units with a high risk of MRSA infection, such as intensive care units and emergency units, because it can protect patients during a period of vulnerability to infection and it can prevent delayed decolonization pending the results of screening [7]. However, in cases of elective surgery like arthroplasty, there is no urgency that requires UD, because patients are not particularly vulnerable and the waiting period for screening results is irrelevant. Moreover, UD as empiric therapy is not recommended because of the risk of increasing bacterial resistance [11]. Prior mupirocin use was reported to increase the risk of mupirocin resistance in MRSA carriers by 9 fold [17]. According to Graber and Schwartz, failure of decolonization may be the result of increased mupirocin resistance [18]. Another disadvantage of UD is financial burden. In this study, mupirocin ointment at 1928.3 yen/product is needed to implement UD for all patients when including personnel costs. In the United States, Stirton et al. reported the cost of empiric treatment with mupirocin for all patients as an estimated $24.65 per patient (equivalent to 2711.5 yen at 110 yen to 1 US Dollar), which included the personnel costs for instruction on mupirocin application [19].
The incidence of deep SSI in THA was reported as 1.1% [20], and the prevalence of revision THA due to PJI was reported as 0.4% following primary procedures and 1.6% following revision hip arthroplasty [21]. Bozic and Ries reported a longer duration of hospitalization with revision arthroplasty for infection than with aseptic loosening (28.2 vs 8.1 days, p<0.001) as well as higher total hospital cost ($96,166 vs $34,866, p<0.001) and higher outpatient charges ($48,348 vs $16,411, p<0.001) [22]. The cost of care for treatment of deep SSI caused by methicillin-resistant strains was estimated at $107,264 compared with $68,053 when caused by sensitive strains [2]. Therefore, revision arthroplasty due to infection is very costly.
Regarding SSI after total joint arthroplasty, MRSA and MSSA were reported as the most common pathogens [23]. Colonization of the nares occurs at higher rates compared with other body surfaces, and 65% of cases of MRSA colonization were detected in the nares [24]. There are three general sources of infection: endogenous, exogenous, and hematogenous [25]. Nasal carriage of S. aureus is thought to be endogenous to patients and is a well-established risk factor for SSI or PJI. The risk of SSI following orthopedic surgery was reported as 6.9 times higher among patients with preoperative MRSA nasal colonization [26] and 2.8 times higher with preoperative MSSA nasal colonization [27]. Thus, because nasal carriage of S. aureus is an important factor for infection, the importance of intranasal decolonization cannot be overemphasized. Mupirocin can eliminate S. aureus nasal carriage in healthy persons for up to 3 months, with a corresponding effect on hand carriage [28]. Treating nasal carriage usually leads to eliminating S. aureus, including MRSA, from other areas of the body [29].
The effectiveness of US for reducing SSI following THA has been widely reported. According to Nixon et al., implementing the US strategy for MRSA eradication reduced the cost of care, considering the enormous costs incurred by revision arthroplasty and prolonged admission due to infection [9]. Hacek et al. implemented US for 1495 cases of total joint arthroplasty with decolonization for S. aureus-positive patients and reported reduced SSI compared with 583 non-screened or decolonized control cases (0.77% vs 1.7%, p≤0.1) [4]. Pofahl et al. reported that the SSI rate of US with decolonization for MRSA-positive patients was significantly lower than that for non-intervention controls (0% vs 0.30%, p=0.04) for total joint arthroplasty [5]. Thus, implementing US can reduce the SSI rate, costs related to revision arthroplasty, and hospitalization duration.
In the present study, there were 6 cases of superficial SSI but no cases of deep incisional SSI or PJI. Among the six superficial SSI cases, 1 was SA+, 5 were SA−, and none were MR+. Although the number of SSIs was overall very low, considering the SA+ rate of 26.9% and SA− rate of 73.1%, the number of SSIs in the SA+ group can be considered very low despite the different risk factors. We decolonize only MRSA-positive patients with mupirocin and treat both nares twice daily for 5 days. At present, we believe that this method is adequate because of the low SSI rate in the MR+ and SA+ groups in this study. However, several reports recommend decolonization in patients who are S. aureus-positive [4] [28] but whether this should be done remains controversial. Further research would be needed to identify patients in whom decolonization should be performed.
In this study, no risk factors were identified for MRSA carriers and only female sex was identified, albeit with low specificity, for S. aureus carriers. Thus, no risk factors that could help with TS were identified. Also, TS was determined not to be as cost-effective as US. UD, which is suitable for intensive care units and emergency rooms, is a more expensive strategy than US for eradicating both MRSA and S. aureus. US would be a more cost-effective strategy than UD for THA patients whose screening results can be waited for. Therefore, overall, US is considered to be the most cost-effective strategy with reduced sampling error rates for THA patients.
There are several limitations in this study. First, the study population included few patients with extremely high risk such as age > 90 years, poorly controlled diabetes, currently undergoing dialysis, and those with human immunodeficiency virus infection. Second, the study had a retrospective design, which means that there was no information available on whether there was a recent history of parenteral antibiotic therapy [30], homosexual activity [31], a recent stay in a nursing home or emergency ward, living with a health care worker, or being a health care worker [32], all of which are putative risk factors for nasal carriage. Third, we attempted to identify risk factors for nasal bacterial carriage in a Japanese population, but different results might be obtained elsewhere. Further investigation is needed to clarify the risk factors for other countries. Fourth, in the calculation of costs, personnel costs would differ considerably depending on the methods used and the insurance systems in place in each country. Fifth, we relied on a nasal culture swab method for determining the presence of MRSA and S. aureus; however, this method has low sensitivity and might introduce false-negative results [6]. For high-risk populations, it is desirable to use more reliable methods, such as polymerase chain reaction, despite their higher cost. Sixth, in order to determine which strategy is the most appropriate, ideally there should have been three intervention cohorts (UD, US, and TS) and a non-intervention cohort (without decolonization). However, there was no UD, TS, or non-intervention cohort in this retrospective study, so we could not provide any comparative data on the incidence of SSI or PJI in these groups. Seventh, although some researchers have emphasized the effectiveness of a bundle protocol consisting of self-administered nasal mupirocin and bathing with chlorhexidine gluconate [33] [34], others have used only nasal mupirocin ointment [4][6]. In this study, we simulated nasal decolonization alone. Moreover, although the nose is considered to be the most important carriage site [28] [29], further investigation is needed to determine whether it is necessary to obtain screening swabs from other body sites. Finally, there were only 6 cases of superficial SSI, 4 of which the causative pathogens did not match the nasal bacteria, and there were no cases of PJI in the 2-year follow-up period. Therefore, the relationship between nasal bacterial carriage and SSI or PJI remains unknown.