In the absence of reliable evidence, it is the opinion of this work group that the following conditions have an unclear effect on risk of PJI:

• Age (conflicting evidence)
• Dementia (imprecise effect estimates)
• Poor dental status (inadequate evidence for a recommendation)
• Asymptomatic bacteriuria (conflicting evidence

Rationale
Out of 143 studies which met inclusion criteria for this recommendation, there were no high strength studies, and only ten were considered moderate strength. The remaining studies were considered low strength. Many of these studies evaluated multiple variables as it applied to either PJI directly, or to other perioperative complications, necessitating the use of various statistical methods to attempt to control for these variables. These methods were frequently constrained in doing so. Additionally, based on the available literature,whether a risk factor is “modifiable” or if optimization of a listed condition affects the risk of infection remained unclear. No specific threshold value could be endorsed for most listed conditions, but instead the simple binary presence or absence of the condition as defined by the individual study criteria affected the risk of PJI. Furthermore, many of the studies were based on national payor databases or registries, whose data is only as accurate as the data being input. As such, there is often no way to verify that an individual diagnosis or the definition of the diagnosis is accurate, though the sheer numbers in such databases may help correct for errors in diagnosis. Finally, definitions and clarity of location of infection introduced ambiguity between studies, some clearly indicating PJI, and others with variations of “deep infection,” “deep surgical site infection,” or “involves deep soft tissue,” among other delineations.

Of the listed and reviewed conditions, obesity was the only risk factor for periprosthetic joint infection that met moderate strength criteria for increased risk of periprosthetic joint infection. The rest are based on single moderate strength and/or low strength studies with either conflicted or limited data, with each condition or risk factor individually discussed below.

No increased risk for PJI, or conflicting data:

Recent UTI and/or asymptomatic bacteriuria

Four low strength studies evaluated the effect of the the presence of asymptomatic urinary tract infection (UTI) on the risk of PJI (Gou, 2014, Honkanen, 2017, Singh, 2015, Sousa, 2014). The Singh and Honkanen studies evaluated bacteriuria, and Gou used leucocyturia as measures of asymptomatic UTI. Only Souza et al found that the odds of PJI were significantly higher in those with asymptomatic bacteriuria (OR 3.95(1.52-10.26)). The other three studies did not show a significant increase in PJI risk. Bozic and associates, in two large database studies (both in 2012, one hip and one knee) attempted to link urinary tract infection to PJI. However, given the nature of the database, “urinary tract infection” (e.g. symptomatic vs. asymptomatic) is not clearly defined, and multiple other variables may be inadequately controlled. The role of symptomatic versus asymptomatic bacteriuria or leucocyturia in the risk of
PJI remains unclear.

Age, dementia and poor dental health
Three moderate strength studies assessed age as a risk factor for PJI, with none indicating increased risk of PJI or infection. The remaining thirty low strength studies demonstrated very mixed results, with some even suggesting a decreased risk of PJI, but most without a difference. There were four low quality studies evaluating the effect of dementia on risk of PJI, all of which found no difference in risk of PJI. However, the confidence intervals were wide and imprecise in the dementia studies (possibly due to low event rates), and therefore the evidence strength was downgraded from limited to consensus. The one low strength study assessing diagnosis of poor dental health showed no difference in risk of PJI (Wu 2014). Despite the lack of evidence individually, the practitioner is encouraged to consider that these may be markers of other comorbidities, which could increase the overall risk of infection or other complication.

POSSIBLE RISKS AND HARMS OF IMPLEMENTATION
Candidacy for surgical intervention is at once, one of the most essential and complex decisions in surgical practice, ethically balancing the degree of pathology and risk of the operation, with the positive benefits to the patient and society at large, in a shared decision-making process between patient and surgeon. The positive effect of indicated lower extremity arthroplasty on quality of life and reduced morbidity is well established. However, its cost to the health care system has been the subject of increased scrutiny. Surgeons are under increasing pressure from payors, health care systems, and peers alike to provide highest value care, balancing the overall cost of care with excellence in patient outcomes. As such, delay or denial of surgical care based on any one or multiple factors in order to avoid one of the most devastating complications of one of the best value surgeries ever practiced should not be taken lightly. Given that all risk factors listed – with the exception of obesity – are supported with only low strength or conflicting evidence, the decision to proceed is individual, and based on myriad other factors, including but not limited to the ability of the system in which the surgeon practices to handle varying degrees of complexity, volume and experience of the surgeon and system, and other confounding factors not herein assessed. Additionally, at this time it is unclear based on the literature if modification of any risk factor, including obesity, actually reduces the risk of PJI. Payors and healthcare systems alike should understand that though tactics to reduce cost may include delaying or avoiding operating on patients with these risk factors, such practice may deny surgery to a much larger proportion of patients who may otherwise significantly benefit and not endure PJI.

FUTURE RESEARCH
Despite the volume of literature addressing risk factors for periprosthetic joint infection, there is a paucity of moderate-quality studies, and complete absence of high-quality studies. Future research must attempt to better control for individual confounding variables prospectively, with better delineation of disease states. For example, though BMI may not be the best measure of obesity overall, its stratification in many studies has helped allow for better comparison between groups, improving the quality of data available. Simply identifying whether or not a disease process is present based off an individual entry of a diagnostic code from the patient’s potentially remote past medical history does not ensure best quality data. Unfortunately, the relatively low incidence of PJI requires large numbers for appropriate statistical power, making registries and large healthcare databases an optimal target for research. Better quality abstraction for such databases is therefore necessary to help de-confound. Additional assessments of markers of disease status and their associated thresholds may also help the clinician further and more accurately stratify risk. Finally, identification of risk associated with a condition or stage of comorbidity does not by itself afford the provider the ability to proselytize for change, as the effect of modification and optimization of the status of a listed condition is still unclear. Future research endeavors should specifically be designed to determine if risk factor modification truly results in a reduction in the risk for PJI after hip or knee arthroplasty surgery. Given frequently conflicting conclusions among studies, the individual system and even provider-specific management of comorbidities – which was typically not delineated – may account for such discrepancies. Prospective, appropriately controlled studies incorporating these considerations will better afford surgeon and patient the ability to predict and potentially minimize risk of periprosthetic joint infection.
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