A definite preoperative diagnosis of periprosthetic infection of a TKA is imperative for proper treatment and management, but it remains a difficult and elusive process because no single test can be used to identify infection. Culture may be affected by multiple factors, including administration of antibiotics [33
], formation of a biofilm [14
], or the inability of standard growth media to isolate rare organisms, all of which could lead to false-negative results; or by contamination, leading to false-positive results. Serologic tests including ESR and CRP have been used as part of the preoperative evaluation for PJI, but their low specificity reduces their diagnostic value [11
]. Numerous combinatorial methods for determining the likelihood of infection have been proposed and found useful in diagnosing PJI [5
]. The most commonly used diagnostic criteria take into account the presence of purulence or a draining sinus, serology, positive culture, and histologic analysis [5
]. We believe the combination of joint aspirate analysis and serology enhances the accuracy of the diagnosis. Our goals were to understand variations in the currently utilized diagnostic criteria and to incorporate synovial fluid WBC count and PMN% into a new set of diagnostic criteria.
This study has a few shortcomings. First, our comparison of the existing diagnostic criteria is hindered because our institution did not perform histologic analysis as part of the workup for PJI. Five of the six criteria sets studied included histologic analysis as a criterion. This limitation was addressed by analyzing each of the criteria sets three times (assuming histology negative, positive, and inconclusive). Second, our criteria were not empirically derived. Although the thresholds we describe are reportedly individually valid thresholds for diagnosing PJI, we recognize the potential for combinatorial variability inherent in development of our diagnostic algorithm and slight variations in the implementation of our algorithm may lead to varying results. Third, despite the prospective collection of some data, we did not perform joint aspirate analysis in every patient as performance of joint aspiration was left to the discretion of the treating surgeon. Fourth, although prior studies have shown similar cutoff values for WBC count and PMN% in hips and knees [13
], all patients in this cohort underwent revision TKA, and the results may not be generalizable to other joints. Fifth, WBC count and PMN% may not be reliable for a patient with inflammatory arthropathy, such as crystalline deposition disease or rheumatoid arthritis, because studies that determined the cutoff values for these parameters (as well as our study) excluded or separately analyzed this category of patients [18
]. Sixth, as has previously been reported [7
], in cases in which the cells in the aspirate are partially clotted or degenerate, reliable cell counts cannot be determined. We excluded these patients from our study and can make no comment on the applicability of our set of criteria in those cases. Finally, our study lacks a known and reliable gold standard for comparison in diagnosing PJI. Instead, we rely on previously published and widely used diagnostic criteria. While this is far from a gold standard definition of PJI, it is necessary to measure our proposed criteria against an existing standard and we could identify no better representation.
Substantial variation existed among the six existing diagnostic criteria sets studied. The variation in some diagnostic criteria when changing the histologic analysis displays the susceptibility of these criteria to false-positive results. Of the five criteria sets employing histology, four had differences in diagnosis when changing histology result from positive to negative. The clinical practice guidelines recently issued by the American Academy of Orthopaedic Surgeons attempt to establish an algorithm for diagnosing PJI [23
]. These guidelines dictate the use of frozen section only in cases where PJI has yet to be discounted or confirmed. The routine use of frozen section was not recommended due to its low sensitivity and high operator-dependent variability. The guidelines also note the inconsistency in definition of positive histology results, which is typically dependent on a neutrophil count per high-power field but is variable among the criteria studied here and the literature [3
]. Large disparity exists among the existing criteria. Assuming positive histology, according to Criteria Set 1, all cases (172) would be septic while Criteria Set 6 diagnoses only 34 as septic. This trend is maintained despite changes in histology outcome. This finding is further displayed by the agreement of determinate results. Assuming inconclusive histology results (Scenario C), only 131 of 172 cases (76%) had complete agreement among the criteria sets that provided a conclusive result (determinate). This is the first known such analysis and provides the evidence that a consensus has not been achieved in diagnosis of PJI.
In an attempt to improve on the diagnostic accuracy for PJI, we developed a new set of diagnostic criteria that included synovial fluid cell count analysis, a factor not included in the other criteria considered. Eighty-seven cases were diagnosed as septic according to the proposed criteria due to positive culture or purulence. Five additional patients were defined as infected solely due to serology or synovial fluid analysis. When excluding indeterminate results due to inconclusive histology, the proposed criteria have 100% sensitivity and high specificity (> 90%) when compared to the six previously published criteria sets and surgeon’s judgment. Of note, specificity could not be calculated when using Criteria Set 1 and Criteria Set 4 as the reference, since all patients not conclusively septic were indeterminate (Table ). Through our subsequent investigation of these “false-positives,” we argue the specificity of our criteria would be higher if measured against PJI, which lacks a true gold standard.
Of the five patients identified as infected by the proposed criteria but aseptic by at least four existing criteria sets, one remains on lifetime antibiotics, one underwent irrigation and débridement within 2 weeks of “aseptic” revision, one developed postoperative drainage suggestive of PJI, and the remaining patients presented with comorbidities justifying the elevated serology. We suggest two of the patients classified as aseptic by at least four of the existing criteria sets were truly infected and identified by the proposed criteria. While cultures were negative in the patient undergoing subsequent surgery, patients undergoing irrigation and débridement for an infected prosthesis at our institution, including this patient, are given perioperative antibiotics, which may have influenced the result of cultures. We believe this patient to have been infected and this patient continues to be treated as such. Comorbidities including sickle cell anemia, chronic renal failure, rheumatoid arthritis, and SLE may have led to increased appearance of infection in these patients [3
]. As such, we recommend, in cases in which a patient’s serology and aspirate results are elevated, patient medical histories be carefully reviewed to determine whether the elevated levels are the result of an underlying pathology. Of course, the difficulty remains in the patients who present with symptoms that raise suspicion of PJI (ie, postoperative drainage or light bacterial growth) and underlying pathologies that justify elevated makers of PJI.
In conclusion, our observations demonstrate a large variation among the currently available diagnostic criteria. Our proposed set of criteria, which incorporates the combination of synovial fluid cell count analysis and serology tests, is 54% to 100% (mean, 94%) sensitive and 39% to 100% (mean: 81%) specific compared to these well-accepted criteria. Especially in the case of elevated ESR or CRP, we recommend the addition of synovial fluid WBC count and PMN% to the standard diagnostic criteria. It is expected these additions will prove useful for diagnosis in research, the postoperative setting, and pre- and intraoperative planning. Our findings underscore the desperate need for establishment and utilization of common diagnostic criteria for PJI to facilitate collaborative PJI research and the confident diagnosis of patients with a failed joint arthroplasty.