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Introduction The aim of the work was to validate the CD15 focus score for the infection pathology of periprosthetic joint infection in a large group and to clarify whether a stratification into low-virulence and high-virulence microbial pathogens is possible by means of the CD15 focus score (quantification of CD15 positive granulocytes). Methods The histopathology of 275 synovial tissue samples taken intraoperatively during revision operations ( n = 127 hip, n = 141 knee, n = 2 shoulder, n = 5 ankle) was evaluated according to the SLIM consensus classification (SLIM = synovial-like interface membrane). Neutrophilic granulocytes (NG) were quantified by the CD15 focus score on the basis of the principle of focal maximum infiltration (focus) with evaluation of one field of vision (about 0.3 mm 2 ). The quantification values were compared with the microbiological diagnoses taking into consideration the virulence groups of low-virulence and high-virulence microbial pathogens and mixed infection. Results The patients with positive microbiological findings ( n = 160) had significantly ( p < 0.001, Mann-Whitney U test) higher CD15 focus score values than patients with negative microbiological findings ( n = 115), the cut-off value being 39 cells per high power field (HPF). The CD15 focus score values of low-virulence microbial pathogens ( n = 94) were significantly lower ( p < 0.001, Mann-Whitney U test) than the values of high-virulence microbial pathogens ( n = 55), the cut-off value being 106 cells per HPF. Based on the microbiological diagnosis the sensitivity with respect to a microbial infection is 0.91, the specificity 0.92 ( PPV = 0.94; NPV = 0.88; accuracy : 0.92; AUC = 0.95). Based on the differentiation of the CD15 focus score values between low-virulence and high-virulence microbes the sensitivity is 0.70 and the specificity 0.77 ( PPV = 0.63; NPV = 0.81; accuracy = 0.74; AUC = 0.74). Conclusion As a result of the high sensitivity and specificity, the easy to use CD15 focus score is a diagnostically valid score for microbial periprosthetic infection. A differentiation between low-virulence and high-virulence microorganism of sufficiently high diagnostic quality is additionally possible as a result of the defined quantification of CD15 positive granulocytes (the CD15 focus score) histopathological diagnosis of microbial infections is possible, which on the one hand supports the microbiological diagnosis and on the other hand by the stratification into low-virulence and high-virulence microbial pathogens could represent an additional basis for a pathogen-specific antibiotic treatment in the event of unclear constellations of findings. [ABSTRACT FROM AUTHOR]